ASUHAN KEPERAWATAN PEMENUHAN KEBUTUHAN OKSIGENASI PADA Tn. S DI RUANG DAHLIA RSUD Dr. SOEDIRMAN KEBUMEN Diajukan Untuk Memenuhi Tugas Akhir Ujian Komprehensif Jenjang Pendidikan Diploma III Keperawatan Disusun Oleh : Arin Dwi Ismawati A01301727 SEKOLAH TINGGI ILMU KESEHATAN MUHAMMADIYAH GOMBONG PROGRAM STUDI DIII KEPERAWATAN 2016
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ASUHAN KEPERAWATAN PEMENUHAN KEBUTUHAN OKSIGENASI
PADA Tn. S DI RUANG DAHLIA RSUD Dr. SOEDIRMAN KEBUMEN
Diajukan Untuk Memenuhi Tugas Akhir Ujian Komprehensif
Jenjang Pendidikan Diploma III Keperawatan
Disusun Oleh :
Arin Dwi Ismawati
A01301727
SEKOLAH TINGGI ILMU KESEHATAN MUHAMMADIYAH GOMBONG
PROGRAM STUDI DIII KEPERAWATAN
2016
ASUHAN KEPERAWATAN PEMENUHAN KEBUTUHAN OKSIGENASI
PADA Tn. SDI RUANG DAHLIA RSUD Dr. SOEDIRMAN KEBUMEN
Diajukan Untuk Memenuhi Tugas Akhir Ujian Komprehensif
Jenjang Pendidikan Diploma III Keperawatan
Disusun Oleh :
Arin Dwi Ismawati
A01301727
SEKOLAH TINGGI ILMU KESEHATAN MUHAMMADIYAH GOMBONG
PROGRAM STUDI DIII KEPERAWATAN
2016
Program Studi DIII Keperawatan
Sekolah Tinggi Ilmu Kesehatan Muhammadiyah Gombong
KTI, Agustus 2016
Arin Dwi Ismawati1, Bambang Utoyo2, M.Kep. Ns
ABSTRAK
ASUHAN KEPERAWATAN PEMENUHAN KEBUTUHAN OKSIGENASI
PADA Tn. S DI RUANG DAHLIA RSUD Dr. SOEDIRMAN KEBUMEN
Latar belakang karya tulis ilmiah ini berdasarkan data yang diperoleh dari (Riskesdas) di
Indonesia khususnya Yogyakarta tahun 2013, prevalensi anemia gizi besi secara nasional pada
remaja usia 13-18 tahun sebesar 22,7%.
Tujuan penulisan karya tulis pada Tn. S di ruang Dahlia RSUD Dr. Soedirman Kebumen
ditemukan masalah keperawatan yaitu ketidakefektifan perfusi jaringan perifer berhubungan
dengan gaya hidup monoton, intoleran aktifitas berhubungan dengan kelemahan umum, defisiensi
pengetahuan berhubungan dengan kurang pajanan. Intervensi dan implementasi yang dilakukan oleh penulis pada masalah keperawatan yaitu
memberikan terapi antibiotik, memberikan transfusi darah PRC, memeriksa vital sign,
mengobservasi adanya pembatasan aktivitas, mengobservasi adanya pembatasan aktivitas, melatih
klien makan sendiri, membantu klien ke kamar mandi, mengkaji pengetahuan klien dan keluarga
tentang penyakit yang dideritaklien,
Hasil evaluasi yang dilakukan 3 diagnosa keperawatan 1 diagnosa yang belum teratasi adalah
ketidakefektifan perfusi jaringan perifer berhubungan dengan gaya hidup monoton.
(7,4 mmol/L)*** NSI = No Significant Interference. A percentage effect ≥ 10% is consideredsignificant interference, **as triolein, LDH = laktat dehidrogenase, P- L =Piruvat = Laktat
(Anonim, 2013)
i. Presisi
Setiap sampel diuji 2 kali per run, 1 atau 2 runs tiap hari, paling sedikit
20 hari.
j. Analytical Range :
Metode ini linier 0 – 1100 U/L untuk serum dan plasma, kondisi auto matis. Rerun
6600 U/L pada ADVIA 1800 untuk serum dan plasma.
k. Nilai rujukan untuk metode ini adalah 208 – 378 U/L.
l. Standarisasi metode ADVIA LDPL didasarkan pada extinction coefficient
NADH. Saat ini tidak ada standar referensi untuk metode ini. Penelitian ini
menggunakan metode piruvat LDH yang mempunyai kelebihan diban dingkan metode
laktat LDH :
i. Yield linearity equal lebih baik dibandingkan metode L-P LDH, sehingga pem-
bacaan spektrofotometer lebih akurat.
ii. Konsentrasi reaktan yang diperlukan lebih rendah sehingga mengurangi cost per
assay.
iii. Reagen solid digunakan untuk mempersiapkan larutan.
iv. Larutan reagen lebih stabil (Krieg et al., 1967)
G. Identifikasi Variabel Penelitian
Variabel bebas pada penelitian ini adalah lama simpan PRC. Variabel lama simpan PRC
ditentukan berdasar waktu simpan darah hari 3, 7, 14, 21, 28, dan 35. Variabel terikat penelitian
ini adalah kadar LDH plasma darah, diukur dengan metode piruvat/NADH. Variabel kadar LDH
plasma darah donor ditentukan berdasarkan nilai rujukan.
H. Definisi Operasional Variabel dan Pengukuran
1. Waktu simpan PRC adalah lama waktu simpan komponen darah PRC mulai dari pemrosesan
PRC dan kemudian dilakukan penyimpanan di bloodbank mulai hari ke- 3, 7, 14, 21, 28, dan
35. Satuan hari. Skala pengukuran rasio.
2. Laktat dehidrogenase adalah enzim yang mengkatalisis reduksi reversibel piruvat menjadi
laktat oleh nicotinamide adenine dinucleotide (NADH) Pemeriksaan yang dilakukan yaitu
LDH dengan metode LDH piruvat/NADH, satuan U/L. Skala rasio. Nilai rujukan LDH pada
orang dewasa 140-300 U/L (Clevenger and Kelleher, 2013).
I. Kontrol Kualitas Internal
Mutu hasil pemeriksaan laboratorium agar dapat dipertanggungjawabkan maka perlu
didahului dengan uji ketelitian (presisi) dan ketepatan (akurasi) analitik. Uji presisi untuk melihat
konsistensi hasil pemeriksaan yaitu kedekatan hasil beberapa pengukuran pada bahan uji yang
sama. Uji presisi dilakukan dengan cara melakukan uji within day dan day to day. Presisi diukur
dengan rerata, simpangan baku (SB) dan koefisien variasi (KV). Rumus SB=√∑d2/2n, sedangkan
rumus KV= [(SB/rerata)x100%], d=selisih, dan n=jumlah sampel. Semakin kecil nilai KV (%),
semakin teliti metode tersebut (Wijono et al., 2004; Linnet and Boyd, 2006).
Uji presisi yang dilakukan pada penelitian ini adalah uji presisi day to day, menggunakan
bahan kontrol yang diukur sebanyak sepuluh hari berturut - turut. Hasil yang didapat kemudian
digunakan untuk menghitung KV dengan menggunakan rumus seperti yang tersebut diatas.
Ketepatan (akurasi) adalah kedekatan hasil pemeriksaan dengan nilai yang sesungguhnya
(true value). Akurasi dinilai dari hasil pemeriksaan bahan kontrol dan dihitung sebagai nilai
biasnya (d%). Rumus d% = [(rerata – NA)/NA], NA = nilai aktual atau sebenarnya dari bahan
kontrol (Wijono et al., 2004; Linnet and Boyd, 2006).
Kalibrasi peralatan sangat diperlukan untuk mendapatkan hasil pemeriksaan laboratorium
yang terpercaya dan menjamin penampilan hasil pemeriksaan. Kalibrasi yang dilakukan adalah
kalibrasi alat ADVIA Chemical Analyzer, spektrofotometer, sentrifus dan pipet. Kalibrasi alat
spektrofotometer meliputi ketepatan pengukuran absorban, ketepatan panjang gelombang,
linearitas alat dan stray light. Kalibrasi sentrifus meliputi kalibrasi revolution per minutes (rpm).
Kalibrasi bloodbank penyimpan PRC dengan thermometer standar.
J. Analisis Statistik
Data karakteristik subyek penelitian disajikan dalam bentuk deskriptif. Distribusi dinilai
dengan menggunakan uji statistik Saphiro Wilk. Perbedaan antar kelompok dinilai dengan
menggunakan independent sample t test jika distribusi data normal atau uji non parametrik jika
distribusi data tidak normal.
K. Prosedur Penelitian
Blangko data diperiksa, dilengkapi peneliti dan selalu dilakukan konsultasi. Semua hasil
pemeriksaan dicatat dan dikumpulkan dalam bentuk formulir terpadu, data yang diperoleh
dianalisis dengan perhitungan statistik dan dimasukkan tabel hasil penelitian.
L. Pertimbangan Etik
Penelitian ini meminta persetujuan komisi etika penelitian biomedis Fakultas Kedokteran
Universitas Sebelas Maret/RSDM di Surakarta dan persetujuan pasien. Pernyataan bersedia
sebagai subyek penelitian diperoleh dengan terlebih dahulu menerangkan secara singkat latar
belakang, tujuan, manfaat penelitian, serta teknik pengambilan sampel darah kepada pasien.
Pasien menandatangani surat pernyataan bersedia menjadi subyek penelitian yang telah
disediakan.
Agustina Westeran Darah Segar SDH Vol.1 No.1
PERBANDINGAN HASIL PEMERIKSAAN LAJU ENDAP DARAH CARA
WESTERGREN ANTARA SAMPEL DARAH SIMPAN DAN
SAMPEL DARAH SEGAR
Oleh
Agustina Dwi Indah V.
Dosen Analis Kesehatan Akademi Analis Kesehatan Malang
INTISARI
Laju endap darah (LED) adalah menurunnya atau mengendapnya sel darah merah dalam
darah dengan antikoagulan yang diukur dengan tingginya kolom plasma yang terbentuk dalam
waktu tertentu dinyatakan dalam millimeter per jam.
Faktor – faktor yang dapat mempengaruhi laju endap darah antara lain faktor eritrosit, komposisi
plasma dan teknik. Dalam hal ini, penggunaan sampel darah yang disimpan tentulah berpengaruh
terhadap nilai LED. Penelitian ini untuk membuktikan apakah ada perbedaan antara hasil
pemeriksaan laju endap darah (LED) cara Westergren pada sampel darah segar dan sampel darah
simpan selama 4 jam. Motode pemeriksaan yang digunakan adalah ”westergren” kemudian
dilakukan pemeriksaan.
Kata kunci: sel darah simpan dan sel darah segar,LED,eritrosit
PENDAHULUAN
Latar Belakang Pemeriksaan darah lengkap merupakan pemeriksaan yang sering di minta oleh klinisi
karena dari pemeriksaan darah lengkap dapat membantu diagnosis penderita. Pemeriksaan darah
lengkap juga dapat digunakan untuk menentukan langkah pemeriksaan selanjutnya atau kemana
penderita itu akan dirujuk. Oleh karena itu, pemeriksaan darah lengkap merupakan pemeriksaan
dasar yang sangat penting dan perlu dilakukan secara cepat dan tepat, sehingga hasil yang
diterima oleh penderita dan dibaca oleh klinisi dapat dipercaya ketepatannya. Laju endap darah
(erithrocyte sedimentation rate, ESR) yang juga disebut kecepatan endap darah (KED) atau laju
sedimentasi eritrosit adalah kecepatan sedimentasi eritrosit dalam darah yang belum membeku,
dengan satuan mm/jam. LED merupakan uji yang tidak spesifik. LED dijumpai meningkat
selama proses inflamasi akut, infeksi akut dan kronis, kerusakan jaringan (nekrosis), penyakit
kolagen, rheumatoid, malignansi, dan kondisi stress fisiologis (misalnya kehamilan). Sebagian
ahli hematologi, LED tidak andal karena tidak spesifik, dan dipengaruhi oleh faktor fisiologis
yang menyebabkan temuan tidak akurat.
Berdasarkan pengamatan peneliti, pemeriksaan darah lengkap pada rumah sakit
ditempat yang lebih maju saat ini sudah menggunakan alat-alat otomatis, sehingga hasil
pemeriksaan darah lengkap dapat diambil segera. Tetapi untuk efisiensi kerja dan kelanggengan
alat yang digunakan, tidak jarang bahan atau sampel darah yang akan digunakan untuk
pemeriksaan darah lengkap tersebut dikumpulkan atau disimpan terlebih dahulu untuk diperiksa
bersamaan. Selain itu,bila hasil pemeriksaan yang ada tidak sesuai dengan keadaan klinis dari
penderita dan timbul keragu-raguan terhadap hasil tersebut, maka pemeriksaan darah lengkap
harus diulang. Bahan atau sampel yang digunakan untuk pemeriksaan ulang ini dapat
menggunakan bahan darah yang masih tersimpan atau bahan darah pengambilan baru. Ditinjau
dari segi penderita, pengambilan yang berulang-ulang menyebabkan penderita merasa kurang
nyaman, sedangkan penggunaan sampel darah yang masih tersimpan sulit diketahui
kebenarannya.
Laju endap darah (LED) adalah menurunnya atau mengendapnya sel darah merah dalam
darah dengan antikoagulan yang diukur dengan tingginya kolom plasma yang terbentuk dalam
waktu tertentu dinyatakan dalam millimeter per jam. Laju endap darah adalah tes yang tidak
spesifik namun masih umum digunakan sebagai indicator penilaian aktifnya suatu penyakit. Oleh
karena itu, laju endap darah masih sering digunakan rutin secara manual. Metode Westergren
adalah metode yang lebih banyak digunakan untuk pemeriksaan laju endap darah.
Faktor – faktor yang dapat mempengaruhi laju endap darah antara lain faktor eritrosit,
komposisi plasma dan teknik. Dalam hal ini, penggunaan sampel darah yang disimpan tentulah
berpengaruh terhadap nilai LED. Untuk mengetahui pengaruh penyimpanan sampel darah
terhadap hasil pemeriksaan LED cara Westergren, maka dilakukan penelitian perbandingan hasil
pemeriksaan LED Westergren pada sampel darah segar dan sampel darah yang disimpan selama
4 jam.
Tinjauan Pustaka
Sel Darah Merah ( Eritrosit ) Darah merupakan komponen esencial makhluk hidup. Dalam keadaan fisiologik, darah
selalu berada dalam pembuluh darah sehingga dapat menjalankan fungsinya sebagai pembawa
oksigen atau oksigen carrier, mekanisme pertahanan tubuh terhadap infeksi dan mekanisme
hemostatis. Darah terdiri dari dua komponen utama, pertama plasma darah yaitu bagian darah
yang sebagian terdiri atas air, elektrolit dan protein darah. Kedua, sel-sel darah merah (blood
corpuscle), yang terdiri atas sel-sel darah merah ( eritrosit ), sel darah putih (leukosit), dan
keping darah (trombosit).
Sel darah merah merupakan sel yang terbanyak beredar dalam darah dengan jumlah
±5x1012 per liter darah. Sel darah merah yang matang berbentuk non-nuncleated biconcave disc,
berdiameter ± 7-8 m dengan ketebalan pada bagian yang paling tebal 2,5 dan pada bagian
tengah (central pallor) 1 m mempunyai kemampuan mengubah bentuk membran, tidak
mengandung organel didalamnya, tetapi mengandung 640.000.000 molekul hemoglobin. Volume
rata-rata sel darah merah adalah 90-95 m. bentuk sel darah merah yang bikonkaf ini
mempermudah sel darah merah merubah bentuk, sehingga dapat melewati pembuluh darah
dengan mudah walaupun diameter pembuluh darah tersebut lebih kecil dari pada sel darah merah,
sel darah merah akan merubah bentuknya menjadi bulat atau sferis dan kemudian
mengembalikan bentuknya menjadi bikonkaf. Fakor yang mempengaruhi sel darah merah untuk
dapat mempertahankan bentuknya masih belum jelas karena sel darah merah dipengaruhi oleh
berbagai kemapuan. Sel darah merah dalam keadaan normal, bila disimpan pada suhu 4C akan
berubah bentuk menjadi relatif sferosit. Perubahan bentuk sel darah merah ini tidak diikuti oleh
perubahan pada volume sehinnga dengan metabolism yang aktif dapat normal kembali. Umur sel
darah merah manusia kurang lebih 120 hari, setelah itu akan dihancurkan. Penghancuran sel
darah merah ini didahului dengan adanya senescence atau tanda-tanda ketuaan dari sel darah
merah dan terjadi beberapa tahapan penghancuran sel darah merah. Penghancuran sel darah
merah dapat terjadi secara ekstravaskuler dan intravaskuler. Penghancuran sel darah merah
ekstravaskuler terjadi ± 80-90% dari penghancuran sel darah merah di limpa. Sedangkan
penghancuran intravaskuler terjadi ±10-20% dari penghancuran sel darah merah di dalam
peredaran darah. Pada aliran darah yang lambat, tampak adanya agregasi sel darah merah di
dalam darah. Dalam keadaan seperti ini, sel darah merah dapat bermacam-macam. Agregasi sel
darah merah dapat terjadi anter sel darah merah sampai beratus-ratus sel darah merah. Pada
aliran darah yang sangat lambat, sel darah merah akan menumpuk dan berjalan dengan perlahan-
lahan. Bentuk seperti ini disebut rouleaux. Didalam pembuluh darah yang besar, agregasi sel
darah merah tersebut akan terurai kembali oleh adanya peningkatan kemampuan melepaskan diri
dari sel darh merah yang lain. Sel darah merah mampu untuk mempertahankan kekuatan dan
fleksibilitasnya. Kemampuan ini tergantung pada struktur protein sitoskeleton dan cara
sitoskeleton berinteraksi dengan lapisan lemak dan membran.
Membran Sel Membran sel darah merah terdiri atas lipid dua lapis atau yang disebut lipid bilayer,
protein membran integral dan suatu langka membran.sekitar 50% dari membran sel darah merah
adalah protein, 40% lemak, dan 10% karbohidrat. Karbohidrat hanya terdapat pada permukaan
luar sedangkan protein perifer atau integral menembus lipit bilayer (Dewi Asih Mahanani, 2002).
Sebagian protein integral membentuk suatu saluran struktural atau pori-pori yang dapat
dilewati oleh bahan-bahan yang hanya terlarut dalam air (selektif permrabel), terutama ion yang
berdifusi antar cairan extracelular dan cairan intracelular. Protein integral juga bekerja sebagai
pengangkut untuk mengangkut bahan-bahan ke arah berlawanan dengan arah difusi yang
sebenarnya, ini disebut transpor aktif. Selain itu terdapat protein parifer yang secara normal
melekat pada protein integral dan tidak menembus membran. Protein perifer ini berfungsi hampir
seluruhnya sebagai enzima tau sebagai jenis pengatur fungsi intracelular. Rangka membran
terbentuk oleh protein-protein struktural yang mencangkup spectrin α dan β, ankyrin, actin,
tropomycin, adducin, tropomudulin, protein 3, protein 4.1, dan protein 4.2 (paladin). Protein-
protein tersebut membentuk jaring horizontal pada sisi dalam membran dan penting untuk
mempertahankan bentuk bikonkaf sel darah merah.
Struktur dasar lapisan lipid bilayer terdiri atas molekul-molekul fosfolipid. Salah satu
bagian dari setiap molekul fosfolipid ini larut dalam air yaitu hidrofilik yang terletak dibagian
luar berhadapan dengan cairan extacelular. Bagian lain hanya larut dalam lemak disebut
hirofobik yang berhadapan dengan sitoplasma. Gugus fosfat dari fosfolipid besifat impermeable
terhadap bahan-bahan yang larut dalam air, seperti ion, glulosa, dan urea. Sebaliknya, bahan-
bahan yang larut dalam lemak seperti oksigen, karbondioksida, dan alcohol dapat dengan mudah
menembus membran ini.
Karbohidrat pada membran umumnya dalam bentuk glikolipid dan glikoprotein,
karbohidrat ini berfungsi meningkatkan hidrofilisitas lemak dan protein, mempertahankan
stabilitas membran oleh adanya struktur yang disebut glikokaliks. Glikolipid yang terdapat pada
membran sel juga berperan dalam reakso imunologis dengan membentuk antigen golongan darah
(Arthur Guyton,1997).
Transport ion dan molekul melalui membran
Transpor melalui membran sel baik secara langsung melalui lapisan lipid bilayer
ataupun melalui protein terjadi salah satu dari dua proses dasar yaitu difusi (yang disebut
transpot pasif) dan transpor aktif. Difusi adalah garak acak antar molekul zat, melalui ruang
intramolekuler pada membran ataupun melalui kombinasi dengan protein integral dari daerah
yang berkonsentrasi tinggi (hipertonik) ke daerah berkonsentrasi rendah (hipotonik). Energi yang
menyebabkan difusi adalah energi kinetik normal dari molekul. Sebaliknya, transpor aktif berarti
gerakan ion atau zat lainnya melintasi membran berkombinasi dengan protein integral melawan
gradien energi yaitu daerah yang berkonsentrasi rendah (hipotonis) ke daerah berkonsentrasi
tinggi (hipertonis). Transport aktif membutuhkan sumber energy secara langsung berasal dari
pemecahan Adenosin Trifosfat (ATP). Mekanisme tranpor aktif yang telah dipelajari secara
sangat rinci adalah pompa natrium-kalium (Na+ -K+ pump) , yaitu suatu proses tranpor yang
memompa ion natrium keluar melalui membrane sel dan pada saat yang bersamaan memompa
ion kalium dari luar ke dalam. Pompa ini terdapat pada seluruh sel tubuh, termasuk sel darah
merah, dan bertanggung jawab atas pemeliharaan perbedaan konsentrasi natrium dan kalium
antara bagian luar dan bagian dalam membran sel demikian juga untuk menetapkan potencial
listrik negatif di dalam sel.
Berikut adalah 3 keistimewaan khusus protein integral yang penting untuk fungsi
pompa Na+ -K+ :
1. Memiliki tiga tempat reseptor untuk mengikatkan ion natrium pada bagian protein yang
menonjol ke bagian dalam sel.
2. Memiliki dua tempat reseptor untuk ion kalium pada bagian luar.
3. Bagian dalam dari protein ini berbatasan atau dekat dengan tempat pengikat natrium yang
memiliki aktifitas ATPase.
Pada saat ion natrium terikat pada bagian dalam protein pembawa, fungsi ATPase pada
protein menjadi aktif. Keadaan ini kemudian akan memecahkan satu molekul ATP menjadi
adenosin difosfat dan membebaskan fosfat energi tinggi yang mengikat energi. Energi ini
kemudian diduga menyebabkan perubahan bentuk pada molekul protein pembawa, mendorong
ion natrium keluar dan ion kalium ke dalam. Mekanisme persis dari perubahan bentuk protein
pembawa ini tidak diketahui (Arthur Guyton,1997).
Mekanisme Pompa Na+ -K
+ dalam Mengatur Volume Sel
Salah satu fungsi terpenting dari pompa Na+ -K+ ialah untuk mengatur volume sel.
Tanpa fungsi pompa ini, banyak sel tubuh akan membengkak sampai kemudian pecah.
Mekanisme yang mengontrol volume tersebut adalah sebagai berikut, di dalam sel terdapat
sejumlah besar protein dan senyawa organik lain yang tidak dapat keluar dari sel. Kebanyakan
dari komponen ini mengandung muatan negative sehingga pada daerah sekitar komponen ini
banyak berkumpul ion positif. Semua komponen ini cenderung menyebabkan terjadinya osmosis
air ke dalam sel. Kalau hal ini tidak dikendalikan, sel akan membengkak sampai pecah.
Mekanisme normal yang mencegah hal tersebut adalah pompa Na+ -K+. pompa ini memompa
tiga ion Na+ ke luar setiap terjadi pemasukan dua ion K+ ke dalam. Selain itu, membran sel
memiliki permiabilitas yang jauh lebih rendah terhadap ion natrium dibandingkan dengan ion
kalium, sehingga keadaan ini memungkinkan ion secara terus-menerus keluar dari sel yang
mencetuskan kecenderungan osmotik berlawanan untuk mengeluarkan air dari sel. Selanjutnya,
bila sel mulai membengkak, hal ini secara otomatis akan mengaktifkan pompa Na+ -K+,
mengeluarkan ion yang masih tersisa ke luar dan membawa air besertanya. Oleh karena itu,
pompa Na+ -K+ mempunyai fungsi unruk menjaga volume sel agar tetep normal (Arthur
Guyton,1997).
Pengaruh Ketidak seimbangan Transpor Na+ -K+ Terhadap Bentuk Eritrosit Pengikatan, transport dan penyebaran oksigen tidak memerlukan energi matabolik oleh
eritosit. Eritosit harus mempunyai energi untuk menjalankan fungsinya dan bertahan di sirkulasi
selama masa hidupnya 120 hari. Selain itu, energi ini diperlukan antara lain :
1. Untuk pengaturan besi dalam hemoglobin.
2. Pengaturan kadar kalium yang tinggi dan rendahnya kalsium dan natrium dalam sel untuk
melawan gradien tingginya kalsium dan natrium serta rndahnya kalium dalam plasma.
3. Mempertahankan reaksi oksidasi pada Metabolisme Pathway.
4. Untuk síntesis lemak dan nukleotida.
Eritrosit secara normal mampu mempertahankan hidupnya selama 48 jam pada suhu
73C tanpa sumber energi dari luar. Glukosa adalah sumber energi eritrosit yang dimetabolisme
melalui dua jalur, yaitu Embden Meyerhof glycolytic pathway dan Hexose Monophosphat shunt.
Sebagian besar energi yang diperlukan eritrosit disediakan oleh Embden Meyerhof glycolytic
pathway. Melalui jalur ini, masing-masing molekul dari glukosa dikatabolisme menghasilkan 2
mol ATP. Namun secara anaerobic glukosa juga dikatabolisme menghasilkan piruvat dan laktat
(Ronald A. Sacher, 1991).
Jika energy (ATP) di dalam sel berkurang, fungsi terpenting pompa Na+ -K+ dalam
mempertahankan atau menjaga volume sel akan terganggu. Pemasukan natrium dan kalsium
dalam sel dan pengeluaran kalium keluar sel mengakibatkan osmosis air ke dalam sel, dengan
demikian eritrosit membengkak mengubah bentuk eritosit dari cakram bikonkaf menjadi sferis.
Laju Pengendapan Darah Laju Endap Darah (Erytrocyte Sedimentation Rate) diperkenalkan pertama kali oleh
Westergern pada tahun 1921. Jika darah dicampur dengan antikoagulan dan diletakkan secara
vertikal, sel darah merah akan mengendap secara gradual dengan angka pengendapan yang
ditunjukkan sebagai jarak (dalam milimeter) dimana eritosit jauh per unit berdasarkan waktu.
Pada kebanyakan orang normal, pengendapan berlangsung lambat. Namun pada beberapa jenis
penyakit, pengendapat berlangsung cepat dan pada beberapa kasus, pengendapan berbanding
lurus dengan beratnya suatu penyakit. Pengukuran angka sedimentasi merupakan pemeriksaan
laboratorium yang mempunyai beberapa fungsi antara lain bertujuan mendeteksi proses
keradangan dan memonitor aktifitas atau perjalanan suatu penyakit.
Investigasi pada mekanisme dititik beratkan pada pengendapan sel darah merah. Secara
umum, laju pengendapan darah dipengaruhi oleh faktor sel darah merah, komponen plasma dan
faktor teknis maupun mekanis.
Faktor sel darah merah meliputi : a. Agregasi sel darah merah
Kecepatan pengendapan secara spontan dari sebuah benda bulat yang jatuh bebas ke dalam
cairan yang ditunjukkan oleh persamaan Stokes seperti berikut :
Comparison of the Hemostatic Effects of Fresh Whole Blood, Stored Whole Blood, and Components After Open Heart Surgery in Children
By Catherine S. Manno, Kathleen W. Hedberg, Haewon C. Kim, Greta R. Bunin, Susan Nicolson, David Jobes, Elias Schwartz, and William I. Norwood
In a double-blind study, we compared the postoperative (post-op) blood loss in 161 children undergoing open heart surgery with cardiopulmonary bypass whose immediate post-op transfusion requirements were met with either very fresh whole blood (VFWB), 24- to 48-hour-old whole blood or reconstituted whole blood (packed red blood cells, fresh frozen plasma [FFP], and platelets). Assignment t o treatment groups was not strictly random but dependent, in part, on the ability of families t o provide directed donors for fresh blood. The three patient groups were comparable with respect to patient age, pre-op coagulation profiles (bleeding time, prothrombin time, activated partial thromboplastin time, platelet count, fibrin split products, fibrinogen, and platelet aggregation tests) difficulty of operative procedures and time spent on CPB. Mean 24-hour post-op blood loss in milliliters per kilogram was 50.9 ? 9.3 in the VFWB group, 44.8 .t 6.0 in the 24- to 48-hour-old group, and 74.2 & 8.9 in the reconstituted group (P = .03). When blood loss was compared in the 93 children less than 2 years of age, mean
HE ACQUISITION OF hemostasis in children who T have undergone open heart surgery (OHS) is an important part of their postoperative (post-op) manage- ment. Bleeding that causes changes of intravascular volume and hemodynamic instability immediately after cardiopul- monary bypass (CPB) can, particularly in the very young child, adversely affect patient outcome. The amount of post-op hemorrhage is a consequence of a complex interre- lationship between the integrity of the surgically revised heart and vessels, pre-existing coagulation defects in the patient, and coagulationdefects induced by CPB. A variety of hemostatic defects have been described in children with cyanotic and acyanotic congenital heart disease including thrombocytopenia, platelet dysfunction, disseminated intra- vascular coagulation, and an abnormality of the von Wille- brand's fa~t0r.I .~ The techniques of CPB alter the coagula- tion system through the obligatory administration of heparin and protamine sulphate as well as by contributing to cellular alterations at the blood-surface interface in the oxygenator and tubing. This contribution results in varying degrees of fibrinolysis, thrombocytopenia, and acquired defects of platelet f~nction.5.~ Preoperative screening has
From the Clinical Laboratories and The Department of Pediahics, Anesthesia and Surgery, The Children's Hospital of Philadelphia; and the University of Pennsylvania School of Medicine, Philadelphia.
Submitted March 20, 1990; accepted October 23, 1990. Address reprint requests to Catherine S. Manno, MD, Assistant
Professor of Pediahics, The Children's Hospital of Philadelphia, Department of Clinical Laboratories, 34th and Civic Center Blvd, Philadelphia, PA 19104.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. section I734 solely to indicate this fact. 0 1991 by The American Society of Hematology. 0006-4971 l91/7705-OO19$3.00l0
blood loss was 52.3 f 10.8 in the VFWB group, 51.7 f 7.4 in the 24- to 48-hour-old group, and 96.2 .+ 10.7 in the reconsti- tuted group (P = .OOl). For subjects who had received recon- stituted blood, 30-minute and 3-hour post-op platelet aggre- gation responses to adenosine diphosphate (10 kmol/L) and 30-minute aggregation response to epinephrine (2.5 p,mol/L) were more depressed than in the VFWB and 24- to 48-hour groups (P < .001, P = .005, and P = .02). Comparison of other post-op coagulation tests could not explain the in- creased blood loss in the reconstituted group. We conclude that the transfusion of <48 hours old whole blood is associ- ated with significantly less post-op blood loss than the transfusion of packed red blood cells, FFP, and platelets in children under 2 years old who underwent complex cardiac surgery. The blood losses associated with the transfusion of VFWB and 24- to 48-hour-old blood are comparable and may be, in part, due t o better functioning platelets. o 199 1 by The American Society of Hematology.
not proved to be a reliable predictor of post-op hemor- rhage." As a result of these hemorrhagic tendencies, the vast majority of pediatric patients who have OHS require blood transfusion, despite the well-recognized complica- tions associated with transfusion of blood products, includ- ing transmission of infections and transfusion reactions. Approaches to limiting the number of donor exposures in adults have included the use of autologous blood and cell salvage techniques." Recent pharmacologic approaches to limiting blood loss after CPB in adults have included the use of 1-deamino-8-D-arginine vasopressin (DDAVP), apro- tinin, and dipymridam~le.'~.'~
Another approach, widely used in adult patients in Japan and Israel, is the transfusion of fresh whole blood.16 The hemostatic advantage of fresh blood over platelet concen- trates has recently been reported in adult patients." The clinical experience of pediatric cardiac surgeons has sug- gested that the severity and consequences of post-op hemorrhage is minimized, particularly in small children who have complex congenital heart disease, if post-op transfusion needs are met with fresh whole blood rather than stored blood components. Blood used within 6 hours of collection has not required refrigeration and contains platelets whose function has not been impaired by exposure to cold." Because the practical difficulties of maintaining a ready supply of fresh blood that has passed requisite screening tests are numerous, and because blood compo- nents are readily available and are thought to be hemostati- cally equivalent to fresh whole blood, the use of compo- nents rather than fresh whole blood has been encouraged by the blood banking community.''
To assess whether the use of fresh blood is associated with improved hemostasis following cardiopulmonary by- pass in infants and children, we performed a double-blind, randomized trial comparing 24-hour blood loss in children whose immediate post-op transfusion requirements were
930 Blood, Vol77, No 5 (March l ) , 1991: pp 930-936
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met with either: Group I: very fresh whole blood adminis- tered less than 6 hours after donation (VFWB); Group 11: whole blood administered 24 to 48 hours after donation; Group 111: a combination of packed red blood cells (RBCs), fresh frozen plasma (FFP), and platelets. These compo- nents, usually transfused individually, were combined for study purposes only.
We also compared post-op coagulation values and results of platelet function studies to see if these measures of hemostasis differed among the treatment groups.
MATERIALS AND METHODS
Informed consent was obtained from the parents of each patient before entry into the study. The experimental protocol was approved by the Committee for the Protection of Human Subjects at the Children’s Hospital of Philadelphia and reviewed by the Compliance Branch of the Sterile Drugs and Biologics Branch of the Food and Drug Administration (FDA) in Rockville, MD. All children (newborn to 21 years old) scheduled for OHS with CPB were eligible for study. The patients had congenital heart disease who required palliative or reparative surgery of varying degrees of surgical difficulty. The technical difficulty and operative risk of all surgical procedures were graded by the attending surgeon as simple, intermediate, or complex (see Table 1).
Randomization Because of limited availability of VFWB from the Blood Bank
and the need to enroll equal numbers of subjects into each treatment group, the following randomization schedule was de- vised. For patients whose parents agreed to participate in the study and were able to provide directed blood donors, two thirds were assigned to Group I (VFWB) and one third were assigned Group I1 (24- to 48-hour-old whole blood) using a series of sealed envelopes. For patients whose parents agreed to participate in the study but were unable to provide directed blood donors, one third were assigned to Group I1 (24- to 48-hour-old blood) and two thirds were assigned to Group I11 (reconstituted). For infants transported to this institution for emergency surgery, assignment to the three treatment groups was made on an equal basis using a separate system of sealed envelopes. For these infants, blood was from non-directed donors.
Preparation of Study Units Blood or blood components were collected into standard blood
collection units containing citrate-phosphate-dextrose-adenine-1 (CPDA-1) solution. Typing and cross-matching were performed in standard fashion. A sample of donor’s blood underwent requisite screening tests for infectious disease transmission including rapid plasma reagin (RPR), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), human immunodeficiency virus antibody (anti-HIV), and alanine aminotransferase (ALT) level. Human T-cell leukemia virus-ID1 (HTLV-IDI) antibody testing was added in March 1989.
VFWB was whole blood less than 6 hours old. VFWB was collected on the day of surgery from a donor who, the day before donation, was prescreened and passed all required donor testing. Study units were kept at room temperature until used or for a maximum of 6 hours. Each transfused unit was screened in the same manner. However, testing was not always completed before transfusion. Release of VFWB before completion of screening tests on that unit was approved by the FDA for study purposes only and is not a routine procedure at this institution.
Intermediate Closure of primum ASD with mitral valve replacement ASD repair with mitral valve replacement ASDNSD patch repair Incomplete AV canal repair Complete AV canal repair Pulmonary valvotomy RV outflow tract augmentation; repair total anomalous pul-
Senning proceduret Patch closure of VSD VSD patch repair with resection coarctation of aorta
monary venous return
Complex Arterial switch Fontan procedure for various forms of single ventricle physi-
Modified Glenn shunt§ Separation of aorta and pulmonary artery with VSD patch
Stage I palliation for hypoplastic left heart syndrome11
ology*
repair (Truncus arteriosus repair)
+Subclavian to pulmonary artery anastomosis. t A n operation used in children with transposition of the great vessels
that redirects the venous return using an intra-atrial baffle of autologous tissue. The baffle directs the pulmonary venous blood across the tricuspid valve into the right ventricle and to the aorta; the systemic venous blood is directed across the mitral valve into the left ventricle and to the pulmonary artery.
*An operation used in children with a single ventricle that separates the pulmonary from the systemic circulation. This procedure is based on the principle that the right atrial pressure is adequate to drive blood through the lung, making a ventricle unnecessary.
§Superior vena cava to right pulmonary artery anastomosis. llPalliative procedure consisting of (1) transection of main pulmonary
artery, (2) creation of neoaorta, and (3) creation of systemic to pulmo- nary artery shunt.
Group ZI. Twenty-four- to 48-hour-old blood was whole blood collected 24 to 48 hours before transfusion and was stored at 4 to 6°C until used.
Group ZII. Reconstituted whole blood contained components of whole blood (one unit each of packed RBCs, platelets, and FFP) which were combined to produce a unit of blood that was visually indistinguishable from standard whole blood. A unit of packed RBCs ( 5 5 days old) was brought from 4 to 6°C to room temperature over a period of 2 hours. The unit was placed on a platelet agitator (Helmer Labs, St Paul, MN) for 10 to 20 minutes before reconstitution. A unit of 2- to 5-day-old random-donor platelets that had been collected and stored in conventional fashion was transferred into a thawed unit of FFP using a plasma transfer set (Fenwal Labs, Deerfield, IL, code 4C2243) to prepare platelet-rich plasma. The platelet bag was rinsed with plasma to reduce the loss of platelets. Platelet-rich plasma was then trans- ferred into an 800-mL size transfer pack unit (Fenwal Labs, code 4R2005). Finally, a unit of RBCs was transferred into the platelet- rich bag. After the transfer was completed and components were well mixed by hand, residual air was expressed into the empty RBC
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bag. The platelet-enriched reconstituted whole blood was stored at 22°C without disturbance for about 1 hour and then placed on a platelet agitator until used. This product was available for transfu- sion when the patient came off CPB and was used within 6 hours of reconstitution. All components were AB0 and Rho(D) group identical.
Administration of Study Units
Two units of RBCs were prepared for each subject. The CPB pump was primed with balanced electrolyte solution and whole blood calculated to produce a final hematocrit of 25% during CPB. At the termination of bypass, heparin effect was reversed with protamine sulphate. From this point on, all volume requirements as determined by blood loss and hemodynamic measurement were met with the assigned study blood. The amount of study blood administered varied according to individual patient needs, and was not a predetermined dose. All study blood was passed through a warmer to bring the temperature to 37°C. The surgeon was blinded to the nature of the blood but the anesthesiologist was not. If clinical complications arose, only the surgeon could ask to break protocol before both study units had been administered.
Measurement of Blood Loss Total blood loss was measured for 24 hours after the study blood
was administered. In the operating room, blood loss was deter- mined by weighing sponges and measuring suction and chest tube drainage. In the intensive care unit (ICU), blood loss was assessed by measuring chest tube drainage.
Laboratory Assessment of Coagulation Bleeding times (Simplate; Organon-Teknika, Durham, NC)
were performed on the volar surface of the forearm immediately pre-operatively, and 30 minutes and 3 hours after administration of protamine sulphate. Blood samples were collected through a flushed arterial line. The following laboratory tests were performed immediately before CPB, and 30 minutes and 3 hours after administration of protamine sulphate: platelet count, prothrombin time, activated partial thromboplastin time (aPlT), fibrinogen, fibrin split products (FSP), FVIII:RAg, and platelet aggregation in response to adenosine diphosphate (ADP) (2 kmol/L), epineph- rine (2.5 pmol/L), collagen (.047 mg/mL), and ristocetin (6 mg/mL).
Platelet counts were determined on a Coulter Plus IV electrical cell counter (Hialeah, FL) from blood collected in EDTA. Pro- thrombin time and a P l T were measured on a Coag-A-Mate X2 (Organon-Teknika). Fibrinogen was measured by the dilute throm- bin time method of Clauss.*’ FSP were detected by latex agglutina- tion technique (Thrombo-Wellcotest Kit; Burroughs-Wellcome, Greenville, NC). vWF:Ag was measured by an adaptation of the quantitative immunoelectrophoresis method of Laurel1 (Helena Laboratories, Beaumont, TX).”
Platelet aggregation induced by ADP (BioData Corporation, Hatboro, PA), epinephrine, collagen (BioData), ristocetin (Aggre- cetin; Bio/Data), and epinephrine were studied using platelet-rich plasma anti-coagulated with 3.8% sodium citrate, stored at room temperature and tested within 60 minutes of collection. Platelet concentration was adjusted to 200,000/1*.L. Changes in optical density of the platelet-rich plasma were measured on a platelet aggregation profiler (BioData). Results are expressed as percent maximum aggregation recorded within 5 minutes of adding stan- dard concentrations of the agonist.
Statistical Analysis
Distributions of age, sex, surgical complexity (simple, intermedi- ate, complex), length of time on bypass, and length of time in circulatory arrest in the treatment groups were compared by x2 tests. Mean blood loss and mean pre-op coagulation studies were compared among the three treatment groups by analysis of variance. When the analysis of variance was significant, (ie, the null hypothesis that the means for the three groups were the same was rejected), pairwise comparisons of the groups were performed using t-tests and the Bonferroni method of adjusting for multiple comparisons. Multiple linear regression was used to investigate the effects of several factors simultaneously on blood loss. Statistical significance was set at .05. All analyses were performed with statistical analysis systems.22
RESULTS
Patient characteristics for each of the treatment groups are found in Table 2. A total of 161 patients were enrolled between March 1987 and July 1989. Fifty-two subjects were in Group I, 57 subjects were in Group 11, and 52 subjects were in Group 111. Four children who died within the first 24 postoperative hours were not included in this analysis. One of these patients died in the operating room and the other three died in the ICU; none of these patients died of overwhelming hemorrhage. Each of the three treatment groups were comparable with respect to age, sex, and percentage of cases in each category of surgical difficulty. The groups were similar in terms of mean bypass time, time of circulatory arrest, and the mean amount of blood transfused per kilogram in the first 24 postoperative hours. Comparison of the means for pre-op coagulation tests (bleeding time, platelet count, prothrombin time, partial thromboplastin time, fibrinogen, FSP, FVIII:RAg, platelet aggregation studies) showed the groups were similar.
Blood Loss Mean 24-hour blood loss in milliliters per kilogram was
50.9 ? 9.3 in Group I, 44.8 ? 6.0 in Group 11, and 74.2 ? 8.9 in Group I11 (f = .03) (Table 3).
Differences in mean blood loss varied among the groups according to the age of the patient. Comparison of mean 24-hour blood loss for the 93 children less than 2 years old showed the transfusion of reconstituted whole blood was associated with 85% more blood loss than either of the other products (f = .001). Comparison of mean 24-hour blood loss for the 68 children greater than 2 years old did not show a significant difference among treatment groups (P = .41).
Differences in blood loss among the groups also varied according to the difficulty of the surgical procedure. For patients whose surgery was simple or of intermediate complexity, no significant differences in blood loss oc- curred. However, for those undergoing complex surgery, blood loss differed significantly, patients in Group I11 having the highest blood loss (f = .01). This difference was even more pronounced when the children less than 2 years old with complex surgery were considered (P = ,002); those
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Mean time 2 SE on bypass (min) Mean time f SE of circulatory arrest Mean volume blood given (Cm3/kg) in 24 h
2.8 f 0.4 (0-8.2)
27 25
11 12 29
86.8 2 6.2 38.1 f 4.3 72.3 2 9.9
3.9 f 0.6 (0-19)
30 27
16 12 29
86.1 f 5.8 43.6 f 4.6 75.5 f 7.8
3.8 2 0.8* (0-20)
36 16
9 12 31
84.2 f 5.lt 37.2 f 3.7$ 97.4 5 9.60
No. of subjects with circulatory arrest 41 42 39
*P = .37. t P = .94. SP = .51. §P = .11.
in Group I11 experienced about twice the blood loss of the other two groups.
When the effects of blood loss of age, surgical complexity, and type of blood product were investigated simultaneously using multiple linear regression, blood product and surgical complexity were statistically significant predictors (P = .02 and P < .001, respectively). Reconstituted blood was asso- ciated with an 18 mLikg increase and 24- to 48-hour-old blood with a 3 mLkg decrease in blood loss compared with
VFWB. Compared with simple surgery, complex surgery increased blood loss by 38 mLikg and intermediate surgery by 4 mL/kg.
Laboratory Evaluation
Changes in bleeding time, platelet counts, prothrombin time, aPlT, fibrinogen, FSP, and FVIII:RAg, which are expected following surgery with CPB, were seen in all
Table 3. Blood Loss [mL/kg) (mean f SE) by Age, Surgical Difficulty, and Both
Group I VFWB
Group II 24-48 h
Group 111 Reconstituted Whole Blood PValue"
BY age All ages (n = 161) 50.9 2 9.3 (n = 52) 44.8 f 6.0 (n = 57) 74.2 f 8.9 (n = 52) .03t
2 2 Y (68) 49.4 f 15.6 (25) 37.2 f 9.7 (27) 24.6 f 6.0 (16) NS <2 Y (93) 52.3 2 10.8 (27) 51.7 f 7.4 (30) 96.2 f 10.7 (36) .001*
By surgical difficulty Simple (36) 16.3f 4.6 (11) 31.2 f 15.2 (16) 15.8 f 7.0 (9) NS Intermediate (36) 24.9 f 6.3 (12) 33.5 f 6.0 (12) 32.9 f 7.2 (12) NS Complex (89) 74.8 f 15.0 (29) 57.1 2 7.6 (29) 107.1 2 11.2 (31) .01§
By age and surgical difficulty Simple No patients Intermediate 27.9 2 9.2 (8) 39.8 2 7.9 (8) 36.2 2 9.8 (7) NS Complex 62.6 f 14.3 (19) 56.1 f 9.6 (22) 110.7 f 11.6 (29) .00211
Simple (22 ) 16.3 f 4.5 (11) 31.2 f 15.2 (16) 15.8 f 6.9 (9) NS Intermediate (22 ) 18.9 f 4.6 (4) 21.0 f 5.0 (4) 28.4 f 11.4 (5) NS Complex (22 ) 98.0 f 34.2 (10) 60.1 f 10.4 (7) 54.8 f 0.2 (2) NS
Abbreviation: NS, not significant. *Significant pairwise differences by the method of Bonferroni were as follows: tll v 111. *I v 111, II v Ill. 011 v 111. 111 v 111, II v 111.
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treatment groups (Table 4). Mean activated clotting times measured 30 minutes after protamine were similar in all treatment groups (P = .92). Thirty minutes after prota- mine, subjects in Group 111 had a longer mean aPTT and a lower mean fibrinogen concentration (P = .06 and .07) in comparison with the other groups. Comparison of other mean post-op laboratory values at 30 minutes and 3 hours showed differences among the groups (platelet counts at both times, prothrombin time at 3 hours, and FSPs at 3 hours). Reconstituted blood was also associated with the most abnormal platelet aggregation studies at 30 minutes in the presence of the agonists ADP, epinephrine, and colla- gen (P < .001, P = .02, andP = .007). ADP-induced aggre- gation at 3 hours was also significantly reduced in the reconstituted group (P = .005).
DISCUSSION
Avoiding excessive hemorrhage after OHS with CPB in children is an important factor in improving surgical out- come. Although many approaches to limiting post-op hem- orrhage have been tried, no single approach has proven uniformly successful. In our study, children less than 2 years old who had complex surgery derived the greatest benefit from whole blood less than 48 hours old. Compared with the repair of simpler defects, complex congenital heart defects require more extensive reconstruction and more time on CPB. These factors result in larger blood lossesz3 putting the patients at higher risk for hemodynamic instabil- ity. Although our pediatric patients always require RBC transfusions following surgery, the use of a product that optimizes hemostasis and thereby decreases blood loss will lessen the amount of blood replacement required following surgery and help to reduce donor exposure. Comparison of blood loss for children older than 2 years old did not show a
difference among the treatment groups. However, this result may be a reflection of an inadequate sample size. The finding for young children was highly significant and corrob- orated the impression of some cardiac surgeons. However, as a larger effect on young children was not a formally stated hypothesis a priori, this finding should be interpreted cautiously.
The randomization method used in this study was forced by institutional practicalities and was adopted to provide study units and to allow enrollment of equal numbers of patients in each treatment arm. Enrollment into Group I required that families provide directed donors of the study blood product and enrollment in Group I11 was for those who could not provide donors. Half of the families of patients in Group I1 provided donors and half did not. The issue of providing donors was not applied to infant subjects; the donor pool at this institution provided these study units. There were small differences in the mean age and sex distributions of the study groups; after statistical adjust- ment for age and sex, the difference in mean blood loss among the groups was still significant. However, the compro- mise forced on the randomization may have led to unequal distribution of unknown patient characteristics among the patient groups and may have affected the outcome.
Many abnormalities in hemostasis that follow CPB have been de~cribed.’~.’~ Although levels of most plasma coagula- tion factors fall below pre-op values (especially Factor V), these reductions are generally not severe enough to be associated with clinical bleeding.z6 We observed prolonga- tion of the mean protime and mean a P l T in all of our treatment groups after CPB. However, the transfusion of reconstituted blood was associated with a longer aPTT at 30 minutes and prothrombin time at 3 hours than either other treatment group. Because the transfusion of FFP is ex-
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pected to deliver amounts of plasma coagulation factors analogous to those found in whole blood,” the cause of these differences is not clear. Although the comparison of mean post-op platelet counts at 30 minutes and 3 hours, prothrombin time at 3 hours, and FSP at 3 hours showed significant differences among the groups, the pattern of these differences does not help to explain increased bleed- ing observed in Group 111, as thrombocytopenia was more pronounced in Group 11, prothrombin times equally pro- longed in Groups I and 111, and FSP was higher in Group I.
The effect of CPB on platelets has been intensively studied. CPB is responsible for a transient decrease in platelet count because of dilution and mechanical platelet damage.9 Platelets become activated as they pass through the bypass apparatus. Clinical bleeding has been reported in association with platelet alpha granule release and decrease in levels of platelet secretory ADP.= In vitro abnormalities include loss of fibrinogen receptors from the platelet surface as well as defective aggregation to ADP, collagen, and ristocetin.2”M Some children with congenital heart disease have decreased platelet aggregation re- sponses to ADP and collagen when studied outside of the peri-op period.’ For the group of patients we studied, in vitro platelet function was normal in all groups before surgery and deteriorated most significantly in the patients who had received reconstituted blood. Mean pre-op bleed- ing times were all within the normal range; the means increased in the post-op period but remained in the normal range. The acquired dysfunction of these already impaired platelets probably contributes to bleeding from sites of surgical damage, despite normal bleeding times.
Mohr et a1 have suggested that blood loss following CPB is the same when patients are transfused with either one unit of fresh blood or 10 units of platelet concentrate^.'^ Lavee et a1 have shown that transfusion of fresh whole blood after CPB gives the same increase in platelet count as six units of platelet concentrates and that the platelets in fresh blood retain better function than those in concen- t r a t e ~ . ~ ~ The platelets contained in VFWB are not subject to the damage inherent in concentrate preparation and stor- age.32 The platelets in our reconstituted product had been prepared and stored as platelet concentrate and undoubt- edly lost some of their function. The standard approach to blood replacement after OHS is to give the element of blood which is lacking. In this study, reconstituted blood contained the components of whole blood that are usually administered separately. The purpose of creating this product was to offer a standard therapy arm while blinding the observer to the nature of the blood product. We acknowledge that this product may not have contained platelets in equal number or with equal function to the platelets in fresher whole blood. Although the platelets in
24- to 48-hour-old blood have not undergone centrifugation and concentration, they have been refrigerated at 4°C for at least 1 day and their function is presumably significantly impaired.” Our study shows that the blood loss associated with the transfusion of VFWB and 24- to 48-hour-old whole blood are the same.
Concern over the use of directed fresh blood has been raised by recent reports of fatal graft-versus-host disease (GVHD) in immunocompetent adult patients who have received viable lymphocytes in a transfusion of fresh blood from a close r e l a t i~e . ’~ .~~ The American Association of Blood Banks has suggested that directed blood donations from first degree relatives be routinely irradiated to mini- mize the threat of GVHD.” Because the bulk of VFWB is drawn from directed donors and processing of this product must occur within 6 hours of donation, the routine procure- ment of directed fresh blood is difficult and, occasionally, incompletely screened blood is requested. Meeting post-op cardiac surgery transfusion needs with 24- to 48-hour-old blood eliminates the need for release of untested, very fresh blood. Day-old fresh blood can be screened for infection and supplied to the operating room more easily and from sources other than directed donors. GVHD is not a risk following transfusion of blood whose lymphocytes have been inactivated with i r r a d i a t i ~ n ~ ~ and this procedure could be routinely accomplished for directed 24- to 48-hour-old fresh blood.
In summary, the transfusion of whole blood less than 48 hours old in children less than 2 years old who had complex OHS was accompanied by significantly less post-op hemor- rhage in comparison with stored blood components. The benefit of fresh blood may be because of the presence of better functioning platelets. We have also found that whole blood less than 6 hours old and whole blood that is between 24 and 48 hours old have a similar hemostatic effect. Older fresh blood can be thoroughly screened for infection, stored for routine and emergency transfusion, and could be irradiated to eliminate the risk of GVHD inherent in very fresh blood from directed, family donors. Our current practice is to use screened, refrigerated 24- to 48-hour-old whole blood for early blood replacement requirements following complex OHS with CPB in children. Another approach to decreasing blood loss after OHS suggested by the results of this study might include finding ways to improve the function of the platelets in stored platelet concentrates.
ACKNOWLEDGMENT
The authors thank Joan Grady and Debbie Jones for secretarial assistance, Dr Morty Poncz for technical assistance, and Drs Alan Cohen, Bruno Manno Jr, Michael Laposata, and Jeffrey Silber for their valuable advice.
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2. Maurer H, McCue CM, Caul J, Still WJS: Impairment in platelet aggregation in congenital heart disease. Blood 40207,1972
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