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Hypercoagulable States

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Presentation on theme: "Hypercoagulable States"— Presentation transcript:

1 Hypercoagulable States
Sheri Ziegler, DO

2 Virchow’s Triad Medication Acquired PICC line Hereditary Port –a-cath
Cancer PICC line Port –a-cath Immobility

3 Forming a clot Platelets Clotting factors
(I, II, V, VII, IX, X, XI, XII, XIII) Fibrin Thrombosis

4 Protein C, Protein S, Antithrombin III
Coagulation Pathways Intrinsic Pathway Extrinsic Pathway IX Tissue Factor + VII Contact TF Pathway X XI TF-VIIa PL Common Pathway XIIa HKa Prothrombin XIa PL IXa VIIIa PL Xa XIII Va (Prothrombinase) Thrombin Protein C, Protein S, Antithrombin III XIIIa Fibrinogen Fibrin (weak) Fibrin (strong)

5 Case 1 35 yr old F presents with painful left leg x 1 week

6 History Trauma Medications Family History Personal History Immobility

7 Deep vein thrombosis Ultrasound

8 Acutely became short of breath
What’s worse Lots of pain Little pain

9 Pulmonary embolism CT scan V/Q scan

10 Pulmonary Embolism

11 Cerebral vein thrombosis

12 Arterial Thrombosis

13 Hypercoagulable States Definition
Clinical situation wherein patients suffer from recurrent venous and/or arterial thrombotic problems or are predisposed to such problems

14 Hypercoagulable States Fine Balance in Hemostatic system
"pro" hemostatic system (procoagulant) "anti" hemostatic system (anticoagulant) perturbations in either system can predispose to clotting or bleeding

15 Hypercoagulable States Acquired Hemostatic Abnormalities
Lupus anticoagulant Nephrotic syndrome DIC Prior thrombosis Immobilization Malignancy TTP Heparin induced thrombocytopenia Myeloproliferative disorders Estrogens Prolonged travel

16 What patients with a thrombosis should you suspect as having a hereditary hypercoagulable state ?

17 Possible Hereditary Defects predisposing to Venous Thrombosis
DVT < age 45 Positive family history Recur without precipitating factors Occurs at atypical site Idiopathic

18 Incidence of Hereditary Coagulation Defects

19 “Hypercoagulable work-up”
Factor V Leiden mutation Genetic test for prothrombin gene mutation Functional assay of antithrombin III Functional assay of protein C Protein S assay Tests for antiphopholipid syndrome

20 Activated protein C Resistance
MOST COMMON ETIOLOGY of hereditary venous thrombosis Variation among different populations 5% European or Caucasian population Rare in African Americans, native American Indians, Asians First described in 1994 Factor V Leiden mutation

21 Protein C, Protein S, Antithrombin III
Cascade Intrinsic Pathway Extrinsic Pathway IX TF Pathway Tissue Factor + VII Contact X XI TF-VIIa PL Common Pathway XIIa HKa Prothrombin XIa PL (Tenase) IXa VIIIa PL Xa XIII Va (Prothrombinase) Thrombin Protein C, Protein S, Antithrombin III XIIIa Fibrinogen Fibrin (weak) Fibrin (strong)

22

23 Factor V Leiden Characteristics
15-20% of patients with venous thromboembolism Recurrent thrombosis, familial thrombosis, thrombosis assoc. with pregnancy or young patients

24 Factor V Leiden heterozygous
First Episode of DVT Relative Risk Incidence/yr (%) Normal 1 0.008 Oral contraceptives 4 0.03 Factor V Leiden heterozygous 7 0.06 FVL + OCP 35 0.3 Factor V Leiden homozygous 80

25 Protein C/S and ATIII Deficiency
All much higher risk of thrombosis Young age multiple VTE Usually life long anticoagulation

26 Protein C, Protein S, Antithrombin III
Cascade Intrinsic Pathway Extrinsic Pathway IX TF Pathway Tissue Factor + VII Contact X XI TF-VIIa PL Common Pathway XIIa HKa Prothrombin XIa PL (Tenase) IXa VIIIa PL Xa XIII Va (Prothrombinase) Thrombin Protein C, Protein S, Antithrombin III XIIIa Fibrinogen Fibrin (weak) Fibrin (strong)

27 Prothrombin gene mutation
First described in 1996 Mutation G20210A (guanine to adenine) Increased thrombosis Increased prothrombin levels 2.8 fold increased risk of thrombosis 0.02%/year risk of thrombosis

28 Protein C, Protein S, Antithrombin III
Cascade Intrinsic Pathway Extrinsic Pathway IX TF Pathway Tissue Factor + VII Contact X XI TF-VIIa PL Common Pathway XIIa HKa Prothrombin XIa PL (Tenase) IXa VIIIa PL Xa XIII Va (Prothrombinase) Thrombin Protein C, Protein S, Antithrombin III XIIIa Fibrinogen Fibrin (weak) Fibrin (strong)

29 CASE 45 yr old F with acute pain in right foot.
Rash located on arms and legs. History of recurrent fetal loss.

30 Arterial Thrombosis Evaluation
Lupus anticoagulant Anticardiolipin antibody Homocysteine levels

31 Antiphospholipid syndrome
A clinical diagnosis characterized by arterial and venous thrombosis and recurrent fetal loss Persistent lupus anticoagulant or anticardiolipin antibodies Thrombocytopenia and livedo reticularis

32 Lupus Anticoagulant Tests
Dilute Russell Viper Venom Time (dRVVT) Elevated PTT Anticardiolipin antibody

33 CASE 80 yr old F with DVT. No previous hx of DVT/PE
Not feeling well recently. Lost 15 pounds in 2 months but, increased abdominal girth.

34

35 Venous thrombosis in cancer
Common (20%) of all patients with cancer Increased risk of recurrent VTE Increased risk bleeding with anticoagulation

36 DVT and Cancer Current evidence does not support extensive search for occult malignancy Pursue signs/symptoms Appropriate screening cancer tests

37 Cancer Screening CBC Chemistry panel Stool for occult blood/colonscopy
PSA and digital rectal exam Mammogram Pelvic examination Urinalysis

38 Now you’ve diagnosed – how do you treat?

39 Therapy of DVT/PE Heparin Warfarin Thrombin inhibtors
Unfractionated (IV) Low molecular weight (SQ) Fondaparinux (SQ) Warfarin Thrombin inhibtors Oral Factor Xa inhibitors Rivaroxaban Apixaban

40 LMWH Mainly Anti-Xa activity with some antithrombin activity
Long duration of action More consistent therapeutic window Not reversible with protamine Included: Enoxaparin (Lovenox) Dalteparin (Fragmin) Tinzaparin (Innohep) Fondaparinux (Arixtra) – only anti-Xa activity

41 Coumadin

42 Warfarin—Mechanism of Action
Vitamin K II Vitamin K Utilization Reduced VII IX X Warfarin

43 Effect of warfarin on clotting factors

44 Kaplan-Meier Estimates of the Probability of Symptomatic Recurrent Venous Thromboembolism among Patients with Cancer Lee, A. et al. N Engl J Med 2003;349:

45 Warfarin—Contraindications
Risk of hemorrhage is greater than benefits of therapy Pregnancy Hemorrhagic tendencies or blood dyscrasias Traumatic surgery with large open areas, recent or contemplated surgery of CNS or eye Bleeding tendencies with active ulceration or overt bleeding Lack of patient cooperation Spinal puncture and procedures with potential for uncontrollable bleeding

46 Long time coming….

47 Thrombin inhibitor Dabigatran (Pradaxa)
Thrombin is key step in thrombosis Turns fibrinogen into clot Activates platelets Activates clotting factors

48 DVT treatment NEJM: 361: , 2009

49 Bleeding

50 Oral Factor Xa inhibitors
Rivaroxaban (Xarelto) Apixaba (Eliquis)

51 DVT treatment

52 Bleeding

53 Duration of Therapy First event with reversible or time limited risk factor 3-6 months Unprovoked VTE At least 6 months Special situations – life long Cancer – until resolved Antithrombin III, multiple genetic defects, antiphopholipid syndrome

54 Accept risk of recurrent disease
6 Months Coumadin INR = Continue

55 Recurrent Venous Thrombosis
Incidence of DVT (%) Years

56 D-dimer and Recurrent VTE (PREVENT)
Patients with 1 prior VTE Patients with >1 prior VTE

57 Oral Direct Xa Inhibitor
Xarelto (Rivaroxaban) Oral agent Do not need to check INR Can not be reversed

58 The End

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