S18C227 - Tests of Hemostasis

Question 1

Site of bleeding gives indication of bleeding diathesis

Answer 1

• mucocutaneous, petechiae, ecchymoses, epsitaxis, GI/GU bleed or heavy perids is characteristic of a platelet d/o
• purpura with thrombocytopenia indicates systemic illness
• bleeding into joint and potential spaces and delayed bleeding is common with coagulation factor deficiencies
• pts with both mucocutaneous and bleeding in deep apces may have DIC (platelet and coag factor abnormality)

Question 2

Thrombus

Answer 2

• DVT/PE
• possibly underlying hypercoagulable state
• acquired hypercoagulable d/o and inherited

Question 3

acquired hypercoagulable d/o

Answer 3

thrombocythemia
polycythemia vera
paroxysmal nocturnal hemoglobinuria
antiphospholipid syndrome
cancer

-can have both arterial and venous thrombi

Question 4

inherited hypercoagulable d/o

Answer 4

• Factor V leiden
• prothrombin mutations
• hyperhomocysteinemia
• protein C and S deficiencies
• antithrombin

-tend to be just venous thrombi

Question 5

normal coagulation formation

Answer 5

• platelet plug forms (primary hemostasis)
• then a cross-link of fibrin is produced over top to strengthen the plug (secondary hemostasis)
• these rxns are counterregulated by the fibrinolytic system to limit the fibrin clot and prevent excessive clot formation

Question 6

Primary Hemostasis

Answer 6

• formation of platelet plug requires:
• normal collagen
• normal platelets
• normal von WF (connects platelets to endothelium via glycoprotein Ib)
• normal fibrinogen (connects platelets to each other via glycoprotein IIb and IIIa)
• occurs in 20sec

Question 7

Tests of primary hemostasis:

Answer 7

-platelet count: 150-300 is normal

in thrombocytopenia bleeding not a problem until platelets

Question 8

Secondary hemostasis tests: PT and INR

Answer 8

PT and INR

• PT 11-13s
• INR 1
• extrinsic clotting pathway factors VII, X, V, prothrombin and fibrinogen
• prolonged PT: warfarin (inhibition of 1972 vit K dependent factors), liver dz (decr factors), Abx that inhibit vit K factors (cefotaxime)

Question 9

Secondary hemostasis tests: aPTT

Answer 9

aPTT: 22-34s

• activated partial thromboplastin time
• intrinsic system
• factors XII, XI, IX, VIII, X, V, prothrombin, and fibrinogen
• prolonged if: heparin, factor deficiencies (factors have to be

Question 10

Secondary hemostasis tests: fibrinogen level

Answer 10

5. 1 – 11.8 μmol/L
   - low in DIC
   - elevated as an acute phase reactant

Question 11

Secondary hemostasis test: mix testing

Answer 11

• performed when an there is an abnormal result on screening test
• pts plasma is mixed with normal plasma and screening is repeated
• if mixing corrects the screening test then one or more factors are deficient
• if mixing does not correct the test then there is an inhibitor present

Question 12

Hemostatic tests: FDP

Answer 12

Fibrinogen degradation products

-

Question 13

Hemostatic test: D-dimer

Question 14

Hemostatic test: factor V leiden

Answer 14

• looks for activated protein C resistance and confirmatory test analyzes DNA sequence of Factor V gene
• screening assay uses aPTT with and w/o added activated protein C
• mutation associated with thromboembolism in people

Question 15

Hemostatic test: antithrombin

Answer 15

• 30-45mg/dL
• measures level of antithrombin
• not vit K dependent
• pts with deficiency require higher doses of heparin for anticoagulation therapy
• deficiency causes thromboembolism in

Question 16

Hemostatic tests: antiphospholipid antibodies

Answer 16

-IgG

Question 17

Hemostatic test: other

Answer 17

• anti-factor Xa - used to monitor LMWH tx, may be elevated in renal dz
• blood smear

Question 18

Secondary hemostasis: coagulation cascade

Answer 18

• final product is cross-linked fibrin

- strengthens platelet plug

Question 19

Fibrinolytic system

Answer 19

• limits size of fibrin clots that are formed
• tPA is released from endothelial cells and is trigger for fibrinolytic process
• tPA = tissue plasminogen activator
• tPA converts plasminogen to plasmin which degrades fibrinogen and fibrin inot FDP and degrades cross-linked fibrin into d-dimers
• antithrombin also inhibits hemostasis by binds factors XIIa, XIa, IXa and thrombin thereby inhibiting them (heparin potentiates this rxn
• protein C and S bind together then inactive Facotrs Va and VIIIa, if there is a mutation in factor V (FVL) this prevents protein C from binding and inhibiting factor V leading to prolonged thrombogenic activity
• therfore defects in antithrombin, protein C/S and FVL lead to hypercoagulable state and increased VTE