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Home , Factor VIII, Factor V Leiden, Protein C deficiency, Protein S, Protein S deficiency, Thrombophilia

Hypercoagulable State Practice Guidelines FOR EDUCATIONAL PURPOSES ONLY Washington State Clinical Laboratory Advisory Council The individual clinician is in the best position to determine which Originally Published November 2005 Reviewed/Revised: Sept. 2007/ May 2008/July 2010 tests are most appropriate for a particular patient

Definition: Hypercoagulable state: balance of the system is tipped toward , due to either acquired or inherited increase in pro-coagulant elements (e.g. pro coagulant) or decrease in anti-coagulant elements (e.g. C deficiency).

Hypercoaguable states are suspected in patients who have: 1)" Spontaneous" thrombosis without obvious associated risk factors 4) Family history of recurrent at an early age. 2) Thrombosis, even with a concomitant risk factor, at an early age (e.g. less than 40) 5) Thrombosis in unusual locations (for example: visceral thrombosis or upper extremity 3) Recurrent thrombosis, especially in different sites thrombosis)

Acquired Disorders and applicable laboratory test Inherited Disorders and applicable laboratory test

Initial testing for all patients: PT, aPTT, TT, , Initial testing for all patients: PT, aPTT, TT, Platelet, Fibrinogen (Refer to Coagulation Guideline for Unexplained Disorders on the reverse side) (Refer to Coagulation Guideline for Unexplained Bleeding Disorders on the reverse side)

1) Antiphospholipid (aPL) Syndrome ( ) 1) Leiden/aPC resistance (most common) Tests: 1:1 mix showing inhibitor Test: aPC (activated ) resistance assay OR DNA analysis for - Hexagonal phase lupus inhibitor assay or dilute Russell viper venom time (dRVVT) both can determine if patient is heterozygote or homozygote Anticardiolipin or anti-beta-2-GPI by ELISA (with titers) 2) Factor II (Prothrombin G20210) polymorphism 2) induced (HIT) in appropriate clinical setting. Two types: Test: Factor II DNA Analysis HIT Type l - usually clinically mild and non-progressive HIT TYPE ll - acute, severe, progressive, immuno-mediated and may develop 3) , Deficiency, or III Deficiency life threating paradoxical thrombosis. Test together with: Protein C activity, Protein S free assay, Test: Antibody (PF4) Antithrombin activity assay

3) Cancer 4) Persistent elevation of factor VIII with normal CRP Test: Use what is general practice for cancer diagnosis based on the clinical Test: Factor VIII activity and CRP presentation

Notes: References: Factor V Leiden/Activated Protein C Resistance, Factor II DNA analysis, antiphospholipid antibody and 1. CAP Consensus Conference XXXVI, Diagnosis Issues in , Nov.2001 HIT testing can be done at any time. 2. Hayes, T; and Thrombosis. Nov 2002 Arch Pathol Lab Med, Vol 126:1387-1390. At time of acute thrombosis: 3. Key, NS, McGlennen RC, Hyperhomocyst(e)inemia and Thrombosis. Nov 2002, 1) Protein C, Protein S, antithrombin may be falsely low due to ongoing thrombosis. If normal, Arch Pathol Lab Med Vol 126: 1367-1373. deficiency is ruled out, if abnormal they should be repeated when the patient is asymptomatic and 4. Tsai AW; Cushman M; Rosamond WD; Heckbert SR; Tracy RP; Aleksic N; Folsom off antithrombotic for 2 weeks. AR. Coagulation factors, markers, and venous thromboembolism: the 2) May identify reactive (not causative) antiphospholipid antibodies. longitudinal investigation of thromboembolism etiology (LITE). Am J Med 2002 Dec 3) Factor VIII is an acute-phase reactant. 1;113(8):636-42.

When on heparin/ coumadin: 1) Antithrombin is decreased 20-30% during heparin . 2) Protein C and S are decreased during therapy.

(Coagulation Guideline for Unexplained Bleeding Disorders on reverse side) PUB #681-NonDOH Coagulation Guidelines For FOR EDUCATIONAL PURPOSES ONLY The individual clinician is in the best position to Unexplained Bleeding Disorders determine which tests are most appropriate for a Washington State Clinical Laboratory Advisory Council particular patient. Originally published: May, 1999 Reviewed: Oct. 2001/Dec. 2004/July 2006/Sept. 2007/May 2008/July 2010

Patient History & Physical Exam Important points to consider in interpreting guidelines: 1) Early onset bleeding () versus late onset (humoral factor deficiency). 2) (effects on circulatory levels) 3) Hereditary and/or personal history of bleeding disorders- possible (autosomal, recessive, dominant, sex-linked).

Basic Coagulation Workup (BCW): aPTT, PT, TT, Fibrinogen, Platelet count

Fibrinogen- PT- Normal PT- Prolonged PT- Prolonged Platelet - Normal TT- Prolonged Low aPTT- Prolonged aPTT- Normal aPTT- Prolonged Decreased Coagulation Platelet- Low TT - Normal Other Tests - Workup Bleeding Normal Patient aPTT 1:1 Mix FVII Deficiency, Add protamin Common Pathway D-Dimer , sulfate Deficiency Possible Causes No or Complete Workup for Deficiency Correction incomplete after 60 Full ·FX, FII (ex: No Isolated Pos Neg a) Mild FVIII correction minutes Correction Warfarin RX, Correction Thrombo- b) VWD type II a/ (immediate (slow Vit K deficiency) cytopenia inhibitor) acting ·FVX II (ex: liver II b (autosomal Antibody inhibition) disease) Heparin dominant) Dysfibr- contamination against DIC c) FX III (auto- bovine inogen somal / recessive) Do Lupus Do Deficiency of: dysfibrinogen d) Fibrinolytic anti- Factor ·F VIII (hemophilia work-up: coagulant VIII A, Type I VWD), ·PAI-1 workup Inhibitor ·F IX (hemophilia B), deficiency (contact workup ·F XI Split ·TPA excess reference. ·F XII (Hageman Products ·Alpha 2 lab) Factor deficiency, antiplasmin No bleeding) deficiency Abbreviations: aPTT: Activated Partial Thromboplastin Time CRP: C-Reactive Protein NOTE: Bleeding time or platelet function assay maybe useful as an additional DIC: Dessiminated Intravascular Coagulation diagnostic tool for familial or acquired platelet disorders such as Von Willebrand’s F: Factor disease or Ticlopidine . In general, it is not a predictor of bleeding for PAI: Plasminogen Activator Inhibitor surgical procedures. PT: TPA: Tissue Plasminogen Activator REFERENCES: Work up extracted from literature and modified by University of TT: Washington Department of Laboratory . VWD: Von Willebrand's Disease (Hypercoagulable State Practice Guidelines on reverse side) PUB #681-NonDOH