To Clot Or not Jason Corbeill PA-C. Thrombus—pathologic blood coagulation –Thrombi “embolize” and travel to new places Clot—the normal coagulation of.
Post on 17-Jan-2016
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To Clot
Or not
Jason Corbeill PA-C
• Thrombus—pathologic blood coagulation– Thrombi “embolize” and travel to new places
• Clot—the normal coagulation of blood in the healthy body
How to make a clot
• Start the clot– Contact factors
(intrinsic)– Tissue factors
(extrinsic)
• Grow the clot in a specific location
• FAST!!!!!
• Stop the clot– There needs to be a
means for modulating clot production
• Destroy the clot– In an orderly fashion
so as not to cause emboli.
• Normally all of these steps are happening simultaneously throughout the body
• However, there can be a problem with any one of these steps resulting in either excess clot formation (hypercoagulable state) or not enough clot formation (bleeding tendency)
The players
• Starter Growers– Clotting factors– Thrombin– Platelets– VWF– Homocysteine– Lupus anticoagulant
• Anticardiolipin Ab• Antiphospholipid Ab
– Vit K– Factor V Leiden
• Stopper Destroyers– Protein C– Protein S– Antithrombin III– Plasmin– Medications such as
• Heparin• Warfarin• Aspirin/plavix
Sources of Bleeding
• Platelet dysfunction:– Petechiae– bruises
• Clotting factor dysfunction:– Hemorrhage
joints
muscles
Sources of Clot
• Reason for the clot
• 1. Too many clotting proteins.
• 2. Abnormal clotting proteins.
• 3. Too little thrombolysis.
• 4. Endothelial damage
• Location of the clot • Arterial = platelet
activation or endothelial damage
• Venous = stasis and factor activation, APS
• Both = abnormal clotting proteins or homocysteine
• Screening tests for hemostasis– CBC/PLT– PT– aPTT– TT
• Tests for prolonged PT or PTT– Mixing studies– Individual factor assays– D-dimer, FDP, fibrinogen-tests for DIC– Lupus anticoagulant– Clot stability assay (F XIII)
• Tests for thrombosis– Protein C&S– Antithrombin III– Factor V Leiden– Homocysteine– Lupus anticoagulant
CASES
Case 1-Mr. D
• 55 y/o male presents with complaint of easy bruising
• Hx?
• PE?
Case 1-Mr. D
• Labs – Cbc normal– PT 20 (12)– PTT 48 (32)– What factor abnormality could cause a
prolonged PT and PTT?
Case 1-Mr D
• Vit K dependent factors:– II, VII, IX, X and protein C and S
Case 1-Mr. D
• Diagnosis: hepatic insufficiency– Lack of production of Vit K– Leads to deficiency of Vit K dependent factors
and protein C and S.
Treat with Vit K (oral, IV, subq)
Case 2-Mr. H
• 35 y/o male presents with chest pain.
• He runs marathons
• Hx?
• PE?
• Cbc normal
• PT normal
• PTT normal
Case 2-Mr. H
Case 2-Mr. H
• What conditions would cause a young, healthy male to be in a hypercoagulable state?– Protein C deficiency– Protein S deficiency– Antithrombin III deficiency– Hyperhomocysteinemia
Case 2-Mr. H
Case 2-Mr. H
• Diagnosis—Hyperhomocysteinemia
• Treatement—vit B6/folate
Case 3-Isabel
• 4 y/o female presenting with rash post URI
• Recent URI lasting 4 days
• Now feels normal
• Little sister is ok
• Hx?
• PE?
Case 3-Isabel
• Labs– WBC 7 (3.5-11.5)– Hgb 13 (12.5-16.5)– PLT 9 (150-300)– PT 11 (12)– PTT 28 (32)
Case 3-Isabel
• ITP-idiopathic thrombocytopenic purpura– Antibodies directed against platelets causing
destruction of platelets in spleenTreatment: platelet transfusion if bleeding or
less than 10k. Steroids/IVIG, splenectomy
? What would you have to include in your differential diagnosis if she was older, had confusion or AMS and creatinine (CR) was 2.5 (elevated)?
Case 4-Mrs. D
• 30 y/o female with metastatic breast cancer
• Admitted for left leg pain, found acetabular bony mets and fractures.
• This am on rounds, noticed left lower extremity edema 2-3+, dusky.
• Labs: CBC, PT, PTT normal
Case 4-Mrs. D
• DVT– Virchow’s triad-hypercoagulable state, venous
stasis, intimal trauma– More Labs: D dimer positive but not very
specific.– Treatment: anticoagulation (put the brakes on
the cascade), elevate, compression stockings, hydration, IVC filter
Case 4-Mrs. D
• Try to avoid this…
Case 5-Howie
• 5 y/o with scalp wound that isn’t healing well-just keeps oozing.
• Has had delayed wound healing all of his life, bled more than expected with circumcision.
• Little brother seems to have similar problem
Case 5-Howie
• Family History: mother’s father died of bleeding ulcer age 49
• PE:
• Labs: – PT 11 (12)– PTT 54 (32)– Cbc normal– More labs?
Case 5-Howie
• Tests for prolonged PT or PTT– Mixing studies– Individual factor assays– D-dimer, FDP, fibrinogen-tests for DIC– Lupus anticoagulant– Clot stability assay (F XIII)
Case 5-Howie• Mixing studies:• Barium sulfate absorbed plasma: • lacks II, VII, IX and X, but • contains I, V, VIII and XIII. • Serum: • lacks I, V, VIII, and XIII, but • contains II, VII, IX and X.
• Modification PTT Ref • Pt + barium sulfate abs plasma 53 (22-34) • Pt + serum 24 (22-34)
Case 5-Howie
• Factor IX deficiency (Hemophilia B)– Factors II and X are in common pathway and
their deficiency would cause both PT and PTT elevation.
– Factor VII is in the extrinsic pathway and it’s deficiency would cause elevated PT as well.
– So it must be factor IX deficiency
Case 5-Howie
• Hemophilia A (factor VIII) deficiency
• Hemophilia B (factor IX) deficiency– X linked recessive– Severity depends on how much factor
Treatment: Factor IX concentrates after wounds and prior to surgery
Case 5-Howie
Case 6-Mrs. R
• 35 y/o female presenting with joint stiffness, right leg pain and edema
• Hx fetal loss x 2
• Maternal grandmother died of “blood clot in the lung” at age 40
Case 6-Mrs. R
– PT 11 (12)– PTT 48 (32)– WBC 12.4 (3.5-11.5) – Hgb 13.3 (12.5-16.5)– PLT 118 (130-440)– RF 126 (0-40)– ANA 1:80 (neg)
Case 6-Mrs. R
• Antiphospholipid Antibody Syndrome?– PTT prolonged in vitro only, patient is actually
hypercoagulable– PTT will not correct with mixing study– Lupus anticoagulant– Check Anticardiolipin Ab– Anti beta 2 glycoprotein-I– ANA positive– Anti ss DNA– Antiphospholipid antibodies
Case 6-Mrs. R
• Treatment: – Heparin to coumadin. – Goal INR over 3.– What about the thrombocytopenia?
• Due to APL Ab binding to phospholipid on platelet cell surfaces.
Case 7-Mrs. KL
• 28 y/o female presents with easy bruising
• Bleeds excessively with dental procedures
• History of menorrhagia
• Pregnant with her first child
• FH significant for bleeding problems– Male and female – Scared because her aunt supposedly died in
childbirth due to hemorrhage
Case 7-Mrs. KL
• Labs:– PT 11.2 (12)– PTT 42 (32)– WBC 11.2 (3.5-11.5)– Hgb 11.2 (12.5-16.5)– PLT 160(130-440)
Case 7-Mrs. KL
• ? Von Willebrands Disease?• Autosomal dominant
– VWF is produced in the endothelial cells and platelets– Promotes platelet adhesion to endothelial cells and
each other– Labs include
• VWF antigen (decreased) – Level of VWF
• Ristocetin cofactor activity (down) – Measurement of the activity of VWF
Case 7-Mrs. KL
• Why is PTT prolonged?– VWF also binds to FVIII to create a complex
which ultimately promotes the conversion of X to Xa.
– Decreased function of F VIII (as in hemophilia A)
Case 7-Mrs. KL
• Treatment:– Factor VIII concentrates– DDAVP (desamino-D-arginine vasopressin)
• Promotes the production of VWF
Case 8-Mr. P
• 22 y/o male hotel clerk presents with chest pain, sob, hemoptysis.
• VS: BP 138/88 R 36 P 96
• Exam: CTA
• ABG– PO2 83 (80-100)– PCO2 26 (35-45)– pH 7.28 (7.36-7.44)
Case 8-Mr. P
• So, Mr. P has a pulmonary embolism.
• CT shows it but you susupected it sooner and have already given him heparin/LMWH.
• Why does he have a PE?
Case 8-Mr. P
• Reason for the clot
• 1. Too many clotting proteins.
• 2. Abnormal clotting proteins.
• 3. Too little thrombolysis.
• 4. Endothelial damage
• Location of the clot • Arterial = platelet
activation or endothelial damage
• Venous = stasis and factor activation, APS
• Both = abnormal clotting proteins or homocysteine
Case 8-Mr. P
• PT 11 (12)
• PTT 29 (24-34)
• CBC normal
Tests for thrombosis– Protein C&S– Antithrombin III– Factor V Leiden– Homocysteine– Lupus anticoagulant
Case 8-Mr. P
• Factor V Leiden– Leiden is an abnormal Factor V protein
• It is unable to be inhibited.• 5% of the caucasian population has Factor V
Leiden (1:20)• Heterozygotes 7x increased risk clot• Homozygotes 80x increased risk of clot
statistic
• 60% of inherited hypercoagulable states are due to:
• Factor V Leiden
• Prothrombin polymorphism
• Mutations of Protein C, S and antithrombin III
Case 8-Mr. P
• Lifelong coumadin
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