Pocket Oncology (Pocket Notebook Series), 1st Ed.

SCREENING TESTS IN HEMOSTASIS

Gabriela Soriano Hobbs and Gerald A. Soff

Clinical Scenarios Suggestive of Bleeding Disorders:

• 1° hemostasis: Mucocutaneous bleeding (Mucosal bleeding, menorrhagia, petechiae, & ecchymoses), suggests thrombocytopenia, plt dysfunction, vWD, or vascular causes.

• 2° hemostasis: Deep and/or delayed bleeding suggests factor deficiency.

Prothrombin Time (PT)

• Measures extrinsic pathway (factor VII) & common pathway (factors X, V, II, & fibrinogen(I)).

• INR compensates for differences in PT assays between labs: INR should ONLY be used for pts on warfarin Rx

Causes of Isolated Prolonged PT

• Vitamin K deficiency – needed for synthesis of factors II, VII, X, IX, & protein C & protein S; causes – poor nutrition, malabsorption & prolonged abx use; deficiency affects factor VII first. More sev. will affect PTT as well.

• Liver disease – clotting factors synthesized in liver. (Sev. liver disease affects PTT as well.)

• Medications

Warfarin – inhibits vitamin K-dependent gamma-carboxylation of coagulation factors

Other anticoagulants  rivaroxaban & apixaban inhibit Factor Xa & dabigatran inhibits thrombin

abx alter gut bacterial flora, interfering w/vitamin K absorption.

Activated Partial Thromboplastin Time (aPTT)

• Measures the intrinsic pathway (factors XII, XI, IX, VIII, prekallikrein, high molecular wt kininogen) & common pathway (factors X, V, II, & I).

Causes of Isolated Prolonged aPTT

• Factor deficiencies, particularly of intrinsic pathway

• Specific inhibitors – ie, VIII (hemophilia A) & IX (hemophilia B)

• Nonspecific inhibitors – antiphospholipid Ab, acquired inhibitors (MM, lymphoproliferative neoplasms), heparin

Combined Prolongation of PT and aPTT

• Deficiency or inhibition of factor(s) in common pathway or multiple factors, DIC, antiphospholipid Ab, adv liver disease (can affect all factors except VIII), dysfibrinogenemia, excessive warfarin anticoagulation or sev. vitamin K deficiency (Mayo Clin Proc 2007:864–873)

Fibrinogen

• Low – A/w bleeding. DIC (↑consumption of coagulation factors & plt), thrombolytic Rx, liver disease (↓synthesis), tx w/L-asparaginase (paradoxically a/w ↑ thrombosis, Leukemia 2012). (Note: Dabigatran & other direct thrombin inhibitors may falsely ↓ fibrinogen assay).

• High – ↑ age, pregnancy, oral contraceptives, disseminated malignancy

D-Dimer

• Product of plasmin-mediated lysis of cross-linked fibrin

• Current gen. of D-dimer assays is VERY specific biomarker indicating the presence of fibrin formation (ie, in vivo clot); sensitive, but not specific for presence of activation of the coagulation system in vivo.

• Negative D-dimer result is useful to R/O VTE (not to r/i).

Common Anticoagulants

Warfarin Reversal

• If no bleeding:

INR 6–10, observe or give vitamin 2.5 mg PO (better than SC or IV)

INR >10 vitamin K 5 mg

• If bleeding: Vitamin K 10 mg IV & FFP 2–4 units every 6–8 h (Annals Int Med 2009;150:293)

Additional Tests

• If w/unexplained high PT or PTT after ruling out causes of prolonged PT & PTT mentioned above, obtain thrombin time, if abnl then perform mixing study

• Mixing study (mixes pt plasma w/nl plasma): Correction = factor deficiency, no correction = inhibitor

• Types of inhibitors: (1) immediate acting inhibitors (often LA, contamination w/anticoagulants), (2) inhibitors requiring 37°C incubation for 60 min (suspect specific factor inhibitor), (3) follow up by ordering LA, specific factor assay, & specific factor inhibitor (Clin Lab Med 2009:229–252). Note: Weak inhibitor may be diluted by nl plasma leading to correction & an incorrect result

Bleeding Disorders With Normal PT/aPTT

• vWD: May have mild FVIII deficiency, not low enough to detect w/elevated aPTT

• Rare bleeding disorders may have nl PT/aPTT:

Factor XIII deficiency (insufficient fibrin cross-linking)

Deficiency of a2-antiplasmin (excessive fibrinolysis)