IVMS-Hematology-Oncology Terminology Summary Table

7/28/2019 IVMS-Hematology-Oncology Terminology Summary Table

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HEMOTOLOGY/ONCOLOGY SUMMARY/mic Page 1 of16

HEMATOLOGY/ONCOLOGY TRMINOLOGYSUMMARY TABLE

Terms Definitions

Platelet - contains dense granules (ADP, calcium) and -granules (vWF,fibrinogen)

- approximately 1/3 of the body's platelet pool is stored in spleen

- life span of 8-10 days

- vWF receptor: GpIb- Fibrinogen receptor: GpIIb/IIIb

Macrophage - Phagocytoses bacteria, cell debris, and senescent red cells and

scavenges damaged cells and tissues- long life in tissues

- activated by -interferon

- can function as APC via MHC II- CD14 surface marker

Eosinophils - bilobate nucleus

- packed with large eosinophilic granules of uniform size

- highly phagocytic for Ag-Ab complexes- produces histamine and arylsulfatase (help limit reaction

following mast cell degranulation)

- causes of eosinophilia: neoplasia, asthma, allergic processes,

collagen vascular diseases, parasites

Basophils - mediates allergic reactions

- bilobated nucleus

- densely basophilic granules contain: heparin (anticoagulant),histamine (vasodilator), and other vasoactive amines, and

leukotrienes (LTD4)

- found in blood

Mast cell - mediates allergic reaction

- degranulation - histamine, heparin, and eosinophil chemotatic

factors

- can bind the Fc portion of IgE to membrane- structurally and functionally similar to basophils

- involved in type I hypersensitivity reactions

- found in tissue

Factor XII - first step of the intrinsic pathway- activated by collagen, basement membrane, activated platelets,

and HMWK (bradykinin precursor)

- activates factor XI and converts prokallikrein to kallikrein


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Kallikrein - activated by factor XII

- converts HMWK to bradykinin (kinin cascade)

- converts plasminogen to plasmin (degrades fibrin)

Bradykinin - part of Kinin cascade, activated by intrinsic coagulation

pathway

- vasodilation- permeability

- pain

Common coagulation

pathway

- X (+V) II (aka thrombin) Fibrin aggregation (by XIII

and Ca2+)

- both extrinsic and intrinsic pathways convert on factor X

Factors effected by VitaminK deficiency Factor II (thrombin, common pathway) Factor VII (extrinsic pathway)

Factor IX (intrinsic pathway) Factor X (common pathway

protein C

protein S- vit K activated by epoxide reducatase cofactor in maturation

of II, VII, IX, X, C, and S from precusors

Antithrombin - activated by heparin

- inhibits thrombin and: factor VII (extrinsic)

factor IX (intrinsic) factor X (common) factor XI (intrinsic)

factor XII (intrinsic)

Protein C - Protein C is activated by thrombomodulin from endothelial cells

- protein S assist activated protein C in the cleavage and

inactivation of Va and VIIIa

tPA - activates plasmin, which degrades fibrin- used as a thrombolytic

platelet plug formation - injury: vWF binds to exposed collagen

- adhesion: platelets bind vWF via GpIb receptor and releaseADP and Ca2+ (necessary for coagulation cascade) - ADP: helps platelets adhere to endothelium, ADP binding to

receptor induces GpIIb/IIIa expression at platelet surface

aggregation: fibrinogen binds GpIIb/IIIa receptors and links

platelets

Aggregation balance - Pro-aggregation factors: TXA2 (released by platelets) blood

flow and platelet aggregation


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- Anti-aggregation factors: PGI2 and NO (released by endothelial

cells) blood flow and platelet aggregation

Drugs that disrupt

thrombogenesis

- aspirin: cyclooxygenase ( TXA2 synthesis)- Ticlopidine and clopidogrel: inhibits ADP-induced expression

of GpIIb/IIIa (platelets can't cross link)

- Abciximab: inhibits GpIIb/IIIa directly

Erythrocyte sedimentation

rate

- acute-phase reactants in plasma can cause RBC aggregation,thereby RBC sedimentation rate

- ESR: infections, inflammatory diseases, malignany

neoplasms, GI disease, pregnancy

- ESR: polycythemia, sickle cell anemia, CHF, microcytosis,hypofibrinogenemia

Pathologic RBC forms:

acanthocyte

(AKA: spur cell)

- liver disease- abetalipoproteinemia


basophilic stippling

- Thalassemia

- Anemia of chronic disease- Iron deficiency

- Lead poisoning


Elliptocyte

- hereditary elliptocytosis


macro-ovalocyte

- megaloblastic anemia (also hypersegmented PMNs)

- marrow failurePathologic RBC forms:

ringed sideroblasts

- sideroblastic anemia


schistocyte

- DIC

- TTP/HUS

- traumatic hemolysis


spherocyte

- hereditary spherocytosis

- autoimmune hemolysis


teardrop cell

- bone marrow infiltration


target cells

- HbC disease

- Asplenia- Liver disease

- Thalassemia


Heinz bodies

- oxidation of iron from ferrous to ferric form leads to

**denatured hemoglobin precipitation and damage to RBC

membrane- -thalassemia

- G6PD deficiency


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Howell-Jolly bodies

- basophilic nuclear remnants found in RBCs

- due to functional hyposplenia or asplenia

Microcytic anemias - Iron deficiency- Anemia of chronic disease (may initially present as normocytic

anemia)

- Thalassemias- Lead poisoning

- Sideroblastic anemia

Normocytic, nonhemolytic

anemias

- Anemia of chronic disease (progresses to microcytic)

- Aplastic anemia

- Kidney disease

Hemolytic anemias -intrinsic - RBC membrane defect: hereditary spherocytosis- RBC enzyme deficiency: G6PD, pyruvate kinase deficiency

- HcC- Sickle cell anemia

- Paroxysmal nocturnal hemoglobinuria

Hemolytic anemias -

extrinsic

- Autoimmune- Microangiopathic hemolytic anemia (MIHA)

- Macroangiopathic hemolytic anemia (MAHA)

- Infections

Megaloblastic anemias - Folate deficiency- B12 deficiency

Macrocytic,nonmegaloblastic anemias - DNA synthesis is impaired-caused by liver disease, alcoholism, reticulocytosis MCV,

metabolic disorders, congenital deficiencies of purine andpyrimidine synthesis and drugs (5-FU, zidovudine, hydroxyurea)

Iron deficiency anemia - microcytic, hypochromic

- iron heme synthesis- Plummer-Vinson: iron deficiency anemia, esophageal web,

atrophic glossitis

- Labs: serum iron

transferrin or TIBC

ferritin % transferrin saturation

-thalassemia - microcytic, hypochromic- defect in -globin gene mutation -globin synthesis

- prevalent in Asian and African populations

- peripheral blood smear: basophilic stippling, target cells, Heinzbodies

- 4 gene deletion = hydrops fetalis, (Hb Barts, 4)


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- 3 gene deletion = HbH disease (4)

- 1-2 gene deletion = no significant anemia

-thalassemia minor - microcytic, hypochromic- point mutations in splice sites and promoter sequences -

globin synthesis

- HbF (22)- peripheral smear: anisocytosis, poikilocytosis, target cells,

schistocytes

- seen in Mediterranean populations

- minor = heterozygote- chain is underproduced

- usually asymptomatic

- Diagnosis confirmed by HbA2 (22) on electrophoresis

-thalassemia major - microcytic, hypochromic-point mutations in splice sites and promoter sequences -

globin synthesis

- HbF (22)- seen in Mediterranean populations

- major = homozygote

- chain is absent severe anemia requiring blood transfusions

-presents with marrow expansion skeletal deformities,Chipmunk facies

HbS/-thalassemia

heterozygotes

- mild to moderat sickle cell disease depending on amount of -

globin production

Lead poisoning anemia - microcytic, hypochromic

- lead inhibits ferrochelatase and ALA dehydratase heme

synthesis, protoporphyrin in blood

- also inhibits rRNA degredation- presents with lead lining the epiphyses of long bones on x-ray,

encephalopathy, erythrocyte basophilic stippling, abdominal

colic, wrist/foot drop and sideroblastic anemia- adults: headache, memory loss, demyelination

- treatment: Dimercaprol, EDTA, and succimer (for kids)

Sideroblastic anemia - microcytic, hypochromic- defect in heme synthesis- Hereditary: x-linked defect in -aminolevulinic acid synthase

gene

- reversible etiologies: alcohol, lead

- peripheral smear: ringed sideroblasts (from iron-ladenmitochondria)

- Labs: iron, normal TIBC, ferritin


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- extravascular hemolysis

- defects in ankyrin, band 3, protein 4.2, or spectrin which are

involved in cytoskeleton and membrane integrity- less membrane spherocytes premature removal by spleen

- labs: MCHC, RDW

- presents with splenomegaly, aplastic crisis (B19 infections),positive osmotic fragility test

- treat with splenectomy

Mean Cell Volume (MCV) - Average **size of red blood cells

- Normal range: 80-100 fL (1 fL = 10-15 L)- Differentiates between

microcytic (MCV < 80)

normocytic (MCV 80-100)

macrocytic (MCV >100) anemias

Mean cell hemoglobin

concentration (MCHC)

- Concentration of Hgb RBC - expresses coloration**

- Normal range: 32-36 g/dL

- Differentiates between hypochromic (MCHC < 32) andnormochromic (MCHC 32-36) anemias

- normochromic cells have a "zone of central pallor" (that white

dot in the middle of the cell) that is no more than 1/3 the diameter

of the red cell.- Hypochromic red cells have just a thin rim of hemoglobin.

Red cell distribution width

(RDW)

- Standard deviation of the MCV

- Tells you how much the RBC differ from each other in size.Anisocytosis

- If they are all pretty similar in size, the RDW is low.

- If some are little and some are big, the RDW is high.- Normal range = 12-13.5%

G6PD deficiency - intrinsic hemolytic, normocytic anemia

- intravascular and extravascular hemolysis

- x-linked- hemolytic anemia follows oxidative stress

- presents with back pain and hemoglobinuria a few days later

Pyruvate kinase deficiency - intrinsic hemolytic, normocytic anemia- extravascular hemolysis- autosomal recessive

- defect in pyruvate kinase ATP rigid RBCs

pyruvate kinase catalyzes pyruvate to lactate

- hemolytic anemia in newborns

HbC defect - intrinsic hemolytic, normocytic anemia

- glutamic acid-to-lysine mutation at position 6 in chain mutation


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- patients with HbSC (1 of each mutated gene) have milder

disease than do HbSS patients

Paroxysmal nocturnal

hemoglobinuria

- intrinsic hemolytic, normocytic anemia- intravascular hemolysis

- complement-mediated RBC lysis

- impaired synthesis of GPI anchor/decay-accelerating factor inRBC membrane

- urine hemosiderin

- complication: thrombosis

Sickle cell anemia -point mutation on -chain (glutamic acid valine at position 6)

- sickling from low O2 or dehydration- complications: aplastic crisis (Parvovirus B19),

autosplenectomy, splenic sequestration crisis, salmonella

osteomyelitis, painful crisis (dactylitis [painful hand swelling],acute chest syndrome), renal papillary necrosis, microhematuria

- treatment: hydroxuria (HbF), bone marrow transplant

autoimmune hemolytic

anemia

- extrinsic hemolytic, normocytic anemia- warm agglutination (IgG) - chronic anemia seen in SLE, CLL,

or with certain drugs

- cold agglutination (IgM) - acute anemia triggered by cold, seen

in CLL, Mycoplasma pneumonia infections, or mononucleosis- usually Coomb's test positive

Erythroblastosis fetalis - seen in newborns due to Rh or other blood antigenincompatibility- mother's Ab attack fetal RBCs

Direct Coomb's test - anti-Ig antibody added to patient's RBCs agglutinate if RBCs

are coated with Ig

Indirect Coomb's test - normal RBCs added to a patient's serum agglutinate if serumhas anti-RBC surface Ig

Microangiopathic anemia - extrinsic hemolytic, normocytic anemia

- intravascular hemolysis- RBCs are damaged when passing through obstructed or narrow

vessel lumina

- seen in DIC, TTP-HUS, SLE, and malignant hypertension- schistocytes on blood smear

Macroangiopathic anemia - extrinsic hemolytic, normocytic anemia- intravascular hemolysis

- prosthetic heart valves and aortic stenosis may also cause

hemolytic anemia, mechanical destruction- schistocyte on peripheral smear

Hemochromatosis - labs:


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serum iron

transferrin

ferritin % transferrin saturation

Acute intermittent

porphyria

- defective heme synthesis that leads to accumulation of heme

precursors- affected enzyme: porphobilinogen deaminase

- accumulation of porphobilinogen, - ALA, uroporphyrin

- presents with painful abdomen, red wine colored urine,

polyneuropathy, psychological disturbance, precipitated by drugs- treat with glucose and heme

Porphyria cutanea tarda - defective heme synthesis that leads to accumulation of heme

precursors

- affected enzyme: Uroporphyrinogen decarboxylase- accumulation of uroporphyrin

- blistering cutaneous photosensitivity

- most common porphyria

PT (prothrombin time) - tests the extrinsic pathway

- factor VII (also I, II, V, and X)

- defect leads to increased time

aPTT (Partial

Thromboplastin Time)

- tests the intrinsic pathway- all factors except VII and XIII

- defect leads to increased timeHemophilia - aPTT

- A: deficiency in VIII- B: deficiency in IX

- macrohemorrhage, hemarthroses, easy bruising

Platelet disorders - defect in platelet plug formation bleeding time-platelet abnormalities microhemorrhages, mucous membrane

bleeding, epitaxis, petechiae, purpura, bleeding time, possible

platelet count- Bernard-Soulier disease, Glanzmann's thrombathenia, idiopathic

thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic

purpura (TTP)Bernard-Soulier disease - defect in platelet plug formation- GpIb defect in platelet to collagen adhesion

- platelet count

- Bleeding time

Glanzmann's

thrombasthenia

- defect in platelet plug formation- GpIIb/IIIa defect in platelet to platelet aggregation

- bleeding time, blood smearshows no platelet clumping


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Idiopathic

thrombocytopenic purpura

(ITP)

- platelet survival

- anti- GpIIb/IIIa antibodies peripheral platelet destruction

- megakaryocytes- bleeding time

- platelet count

Thrombotic

thrombocytopenic purpura

(TTP)

- platelet survival- deficiency of ADAMTS 13 degradation of vWF multimers

platelet aggregation and thrombosis

- Labs: schistocytes, LDH

- presents with pentad of neurologic and renal symptoms, fever,thrombocytopenia, and microangiopathic hemolytic anemia

- platelet count

- bleeding time

von Willebrand's disease - vWF carries and protects factor VIII, connects GpIb of plateletto collagen

- defect of intrinsic pathway, vWF may see aPTT

- defect of platelet adhesion to collagen bleeding time- mild, but most common bleeding disorder

- treatment: desmopressin (releases vWF stored in epithelial cells)

DIC - wide spread activation of clotting leads to a deficiency in

clotting factors bleeding state- caused by sepsis (G (-)), trauma, obstetric complications, acute

pancreatitis, Malignancy, Nephrotic syndrome, Transfusion

- Labs: schistocytes, fibrin split product (D-dimer), fibrinogen, factors V and VII

Factor V Leiden - production of mutant factor V that cannot be degraded by

protein C

- most common cause of inherited hyprcoagulability

Prothrombin gene mutation - leads to hypercoagulable state

- mutation in 3' untranslated region associated with venous clots

Antithrombin deficiency - leads to hypercoagulable state- inherited deficiency of antithrombin

- reduced in PTT after administration of heparin

Protein C or S deficiency - leads to hypercoagulable state- ability to inactivate factors V and VIII- risk of thrombotic skin necrosis with hemorrhage following

administration of warfarin

Blood transfusion therapy:

packed RBCs

- Hb and O2 carrying capacity

- acute blood loss and severe anemia


platelets

- platelet count

- usually given in 6 platelet units for therapeutic effect


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- stop significant bleeding (thrombocytopenia, qualitative platelet

defects)


Fresh frozen plasma

- coagulation factor levels by about 20%- treats DIC, cirrhosis, warfarin over-anticoagulation


cryoprecipitate

- contains fibrinogen, factor VIII, factor XIII

- treats coagulation factor deficiencies involving fibrinogen and

factor VIII

Blood transfusion risks - infection

- reactions

- iron overload

- hypocalcemia - citrate is a calcium chelator

- hyperkalemia - RBCs may lyse in older blood unitsHodgkin's lymphoma - Reed-Sternberg cells (CD30+/CD15+)

- localized to single group of nodes- contiguous spread

- constitutional signs/symptoms - low-grade fever, night sweats,

weight loss- mediastinal lymphadenopathy

- 50% of cases associated with EBV

- bimodal age distribution

- more common in men except the nodular sclerosing type(lacunar variant of RS cells)

- good prognosis = lymphocytes, RS cellsNon-Hodgkin's lymphoma - may be associated with HIV and immunosuppression

- multiple peripheral nodes- extranodal involvement common

- noncontiguous spread

- majority involve B cells (except for those of lymphoblastic Tcell origin)

- fewer constitutional signs/symptoms

- peak incidence for certain subtypes at 20-40 years

Nodular sclerosing

Hodgkin's lymphoma

- most common type (65-75%)

- variant type RS cells

- increased # of lymphocytes- excellent prognosis- collagen banding, women >men, primarily young adults

Mixed cellularity Hodgkin's

lymphoma

- lots of RS cells

- increased lymphocytes

- intermediate prognosis- 25% of Hodgkin's lymphoma cases

Lymphocyte predominant - seen in males under 35


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Hodgkin's lymphoma - some RS cells, lymphocytes

- excellent prognosis

- 6% of Hodgkin's lymphoma cases

Lymphocyte depleted

Hodgkin's lymphoma

- slight increase in lymphocytes

- RS high relative to lymphocytes

- seen in older males with disseminated disease- poor prognosis

Burkitt's lymphoma - non-Hodgkin's lymphoma

- seen in young adults

- genetics: t(8;14) c-myc gene moves next to heavy-chain Ig gene

- "starry-sky" appearance - sheets of lymphocytes withinterspersed macrophages

- EBV

- Jaw lesion most common, pelvis or abdomen in sporadic form

Diffuse large B-cell

lymphoma

- non-Hodgkin's lymphoma

- usually seen in older adults, 20% in kids

- most common NHL- may be of mature T cell origin (20%)

Mantle cell lymphoma - non-Hodgkin's lymphoma, B cell

- seen in older males

- genetics: t(11;14) overexpression of cyclin D regulatory gene- CD5+

- poor prognosisFollicular lymphoma - non-Hodgkin's lymphoma, B cell

- seen in adults- genetics: t(14;18) bcl-2 expression inhibits apoptosis

- difficult to cure, indolent course

Adult T cell lymphoma - non-Hodgkin's lymphoma, T cell- seen in adults

- caused by HTLV-1

- adults present with cutaneous lesions- especially effects populations in Japan, West Africa, and the

Caribbean

- aggressiveMycosis fungoides/Sezary

syndrome

- non-Hodgkin's lymphoma, T cell- seen in adults

- adults present with cutaneous patches/nodules

- indolent CD4+

Multiple myeloma - monoclonal plasma cell (fried egg appearance) cancer that arisesfrom the marrow and produces large amounts of IgG (55%) or

IgA (25%)


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- most common 1 tumor arising within bone in the elderly

- intracytoplasmic inclusions containing Ig

- CRAB: hyperCalcemia

Renal insufficiency

Anemia Bone lytic lesions Back pain

(distinguish from Waldenstrom's macroglobulinemia M spike

= IgM, and no lytic bone lesions)

MGUS - monoclonal gammopathy of undetermined significance- monoclonal plasma cell expansion without symptoms of

multiple myeloma

Leukemias - unregulated growth of leukocytes in bone marrow

- or number of circulating leukocytes in blood and marrowfailure

- anemia, infections, & hemorrhage

- leukemic cell infiltrates in liver, spleen, and lymph nodes arepossible

ALL - Acute lymphoblastic

leukemia/lymphoma

- usually seen < 15 y/o

- may present with BM involvement in children or mediastinal

mass in adolescent males- BM replaced by lymphoblasts

- TdT+ (marker of pre-T/B cells)

- CALLA+- most responsive to therapy

- may spread to CNS or testes

- genetics: t(12;21)

SLL - small lymphocytic

lymphoma/CLL - chronic

lymphocytic leukemia

- usually seen > 60 y/o- often asymptomatic

- smudge cells in peripheral smear

- warm antibody autoimmune hemolytic anemia- SLL is same as CLL except CLL has peripheral blood

lymphocytes

Hairy cell leukemia - seen in adults- Mature B cell tumor in elderly- cells have filamentous hairlike projections

- stain TRAP (tartrate-resistant acid phosphatase) positive

AML - Acute myelogenous

leukemia

- seen in 60 y/o

- Histo: Auer rods in cytoplasm- circulating myeloblasts on peripheral smear

- genetics: t(15;17) M3 AML (acute promyelocytic leukemia)


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responds to all-trans retinoic acid (vitamin A), which induces

differentiation of myeloblasts

- DIC is common presentation

CML - Chronic

myelogenous leukemia

- 30-60 y/o

- Philadelphia chromosome - t(9;22), bcr-abl

- JAK2 mutation?- myeloid stem cell proliferation

-presents with RBC, neutrophils, metamyelocytes, basophils,

platelets; splenomegaly

- may accelerate and transform to AML or ALL (blast crisis)- very low leukocyte alkaline phosphatase due to immature

granulocytes

- treat with imatinib

Auer bodies - peroxidase-positive cytoplasmic inclusions in granulocytes andmyeloblasts

- commonly seen in acute promyelocytic leukemia (M3)

- treatment of AML M3 can release Auer rods DIC

Langerhans cell

histiocytosis (LCH)

- proliferative disorder of dendritic (langerhans) cells from

monocyte lineage

- etiology unknown

- cells are functionally immature and do not efficiently stimulateT lymphocytes

- cells express S-100 and CD1a

- Birbeck granules (look like tennis rackets on EM)

Polycythemia vera - chronic myeloproliferative disorders

- abnormal clone of hematopoietic stem cells are increasingly

sensitive to growth factor

- RBCs ( plasma volume, RBC mass)- WBCs

- platelets

- genetics: JAK2+

Essential thrombocytosis - chronic myeloproliferative disorders

- similar to polycythemia vera, but specific for megakaryocytes

- platelets- genetics: JAK2+ (30-50%)

Myelofibrosis - chronic myeloproliferative disorders

- fibrotic obliteration of BM

- teardrop cells in blood smear

- RBCs- variable amounts of WBCs

- variable amounts of platelets


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- presents with achlorhydria (lack of gastric acid) due to parietal

cell destruction, chronic gastritis, increased risk of gastric

carcinoma, elevated serum gastrin, and signs of vitamin B12deficiency

IVMS-Hematology-Oncology Terminology Summary Table

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