Defects in Coagulation (Part 1) Flashcards

Question

What causes decreased platelet production?

Answer 1

– Nutritional: Vitamin B12 deficiency ``` – Marrow failure or disease • Aplastic anemia • Myelodysplasia or Leukemia • Congenital thrombocytopenia syndromes • Marrow replacement (metastatic Ca, Gaucher’s) • Toxin/Drug/Irradiation ```

Answer 2

– Non-immune: Blood Film often abnormal √ • Disseminated intravascular coagulation – Immune • Fab mediated: Blood Film usually normal – Immune thrombocytopenic purpura (ITP), Antiphospholipid syndrome • Non-Fab mediated – Heparin-induced thrombocytopenia), Immune complex disease (HIV), TTP • Innate immunity – Sepsis √

Answer 3

Childhood and adult

Answer 4

– Abrupt onset of severe thrombocytopenia – Antecedent viral syndrome is common – Mechanism: Auto-antibody to platelet surface glycoproteins – Decreased platelet survival and marrow usually shows normal to increased numbers of megakaryocytes – Most patients recover: 50% recover within 6 weeks, 80-90% recover within 6 months

Answer 5

– Onset usually insidious • Minor bleeding, menorrhagia, bruising usually no obvious antecedent viral illness – Decreased platelet survival, but most also have decreased production, despite marrow that has megakaryocytes – Only 5% have spontaneous recovery

Answer 6

Blood Film: RBC and WBC usually normal with large platelets due to high turnover rate

Answer 7

Heparin-Induced Thrombocytopenia

Answer 8

Timing consistent with immune: 4-10 days into heparin therapy

Answer 9

* Moderate thrombocytopenia (rarely < 20,000/ul) – Suspect if platelet count falls by half * Associated with thrombotic events– Increases risk for thrombosis 20-40 fold

Answer 10

Suspicion, Lab confirmation: PF-4~Heparin ELISA or SRA

Answer 11

– Stop all heparin therapy | – Begin alternative anticoagulation • Direct Thrombin Inhibitor (DTI): Argatroban, Bivalirudin

Answer 12

Thrombotic Thrombcytopenic Purpura (TTP) Hemolytic uremic syndrome (Shiga-toxin associated-HUS, etc.) DIC, sepsis

Answer 13

– Lab abnormalities (required for diagnosis) • microangiopathic hemolytic anemia • thrombocytopenia – Organ dysfunction (not required for diagnosis) • renal failure • mental status changes • Fever TTP is a clinical diagnosis

Answer 14

ADAMTS13 is an enzyme that regulates VWF/platelet interactions Acquired autoantibody or congenital

Answer 15

Plasma Exchange

Answer 16

Screen for platelet and VWF function via Aperture closure time used when there is prolonged or strong bleeding history positive test can mean VWD

Answer 17

* Support platelet adhesion to exposed collagen (at sites of injury). * Serve as carrier for Factor VIII – vWF maintains factor VIII in circulation. Thus: abnormalites of vWF may lead to F-VIII deficiency (long PTT).

Answer 18

assay vWF – Quantitation of VWF by immunoassay by VWF:Ag – Quantitation of VWF function by Ristocetin cofactor assay with VWF:RCo

Answer 19

Bernard Soulier syndrome

Answer 20

Glanzman’s thrombasthenia

Answer 21

Tissue factor, phospholipid and calcium are added to citrated plasma and clotting time is measured. Reported in seconds and INR. measures extrinsic pathway (factor 7 and on)

Answer 22

Mathematic calculation: – Normalizes reported prothrombin time so that result is comparable across laboratories. – Intended for warfarin monitoring

Answer 23

Surface activator, phospholipid and calcium are added to citrated plasma and clotting time is measured measures intrinsic pathway (factor 11 and on)

Answer 24

Patient plasma is mixed with normal plasma containing 100% of all factors. Clotting time is performed on the mixed sample – If the clotting time corrects to normal, then a factor deficiency is likely –If the clotting time remains prolonged, then an “inhibitor” is likely

Answer 25

Intrinsic pathway defect – Factor VIII, IX, XI, XII, Contact factors – von Willebrand disease if factor 8 is low Inhibitors: – Heparin: accelerates antithrombin – Lupus anticoagulant: Inhibits phospholipid dependent reactions – Specific factor inhibitor

Answer 26

repeat PTT and a 1:1 mix if mix corrects then assay factors 8, 9, 11 and 12 since one is deficient

Answer 27

• Factor deficiency: – Factor VII – Combination of factors: Vitamin K deficiency/Oral anticoagulant or Liver Disease • Inhibitors: – Factor inhibitor – Lupus inhibitor (rare presentation)

Answer 28

repeat PT and 1:1 mix if mix corrects (deficient), test liver function, factors 2,7, 5 and 10 and vitamin K level

Answer 29

Factor Deficiency: – Isolated factor: X, V, II, fibrinogen (common path) – Multiple factor deficiency from Liver disease, Vitamin K deficiency or DIC Inhibitors: – Isolated factor inhibitor (X, V, II) – Drugs: Heparin, Direct Thrombin Inhibitors – Lupus inhibitor

Answer 30

factor 8 | Physiologic anticoagulants: Antithrombin, Protein C, Protein S and Factor V Leiden

Answer 31

If you can see blood = mucocutaneous If you cannot see blood = deep (muscle, joint, etc)

Answer 32

mucocutaneous

Answer 33

CBC with dif Coagulation studies (PT and PTT) Peripheral blood smear

Answer 34

wait and see with kids if severe or adult usually need steroids or IVIG

Answer 35

DIC which is an acquired syndrome characterized by systemic intravascular coagulation which causes consumptive bleeding disorder

Answer 36

correct underlying cause! then fresh frozen plasma and platelet transfusion

Answer 37

joint, muscle, soft tissue, intracranial -- all deep