Montepara Venous Thromboembolism

Venous Thromboembolism (VTE)

Clot formation in venous circulation

Manifests as deep vein thrombosis (DVT) or pulmonary embolism (PE)

Risk factors for VTE

Increasing age

History of VTE

Blood stasis → immobility, paralysis, obesity

Vascular injury → surgery, trauma, venous catheters

Hypercoagulability → cancer, coagulation factor abnormalities (i.e. Protein C, Protein S), antiphospholipid antibodies, pregnancy, certain drugs (estrogen/testosterone related drugs, heparin)

What is Virchow’s Triad?

Blood stasis

Vascular injury

Hypercoagulability

Clinical presentation of DVT

Unilateral leg swelling

Pain

Tenderness

Erythema

Warmth

Clinical presentation of PE

Cough, chest pain or tightness, shortness of breath

Palpitations, dizziness

Hemoptysis (coughing up blood)

Tachypnea, tachycardia

Diaphoresis

Cyanosis

Hypotension

Shock

Diagnosis of VTE involves _____

D-dimer blood test

• Measures fibrin clot degradation product

• Good negative predictive measure, bad positive predictive measure

  • Negative → no clot

  • Positive → maybe a clot, maybe something else → go to next step

• Compression ultrasound (noninvasive) or venography (more accurate, invasive, expensive)

Nonpharmacologic prevention of VTE

Ambulation (walking)

Compression stockings

Intermittent pneumatic compression (IPC) devices

• Most effective when worn for at least 18 hours/day

Inferior vena cava (IVC) filters

Recommendation for IVC filters to prevent VTE

Recommended for short term use ONLY in patients with lower half of body DVT, high risk of PE, and who can’t be on anticoagulation

Main pharmacologic strategy for prevention of DVT

Anticoagulation

Pharmacologic treatment of VTE

Anticoagulation is mainstay

Thrombolytic therapy in select cases

What anticoagulants can be used for both VTE prophylaxis and treatment?

UFH

Enoxaparin

Apixaban

Rivaroxaban

Fondaparinux

Dabigatran

What anticoagulant can be used for VTE prophylaxis ONLY?

Dalteparin

What anticoagulants can be used for VTE treatment ONLY?

Edoxaban

Warfarin

Dosing of UFH for VTE prophylaxis

5000 units SC q8-12h

Dosing of UFH for VTE treatment

80 units/kg IV bolus followed by 18 units/kg/hr IV infusion

Contraindications for UFH

Uncontrolled active bleeding

Severe thrombocytopenia

History of HIT

Hypersensitivity to pork

Adverse Effects of UFH

Bleeding

Thrombocytopenia

HIT

Hyperkalemia (blocks aldosterone synthesis)

Monitoring for UFH

aPTT or anti-Xa

• Monitor safety and effectiveness to help determine dose

• Anti-Xa is more accurate but more expensive

Platelets

Hemoglobin

Hematocrit

What abnormality in hemoglobin and hematocrit indicated internal bleeding?

Decrease

Dosing of enoxaparin for VTE prophylaxis

30 mg SC q12h OR 40mg SC daily

If CrCl < 30 mL/min

• 30 mg SC daily

Dosing of enoxaparin for VTE treatment

1 mg/kg SC q12h OR 1.5 mg/kg SC daily

If CrCl < 30 mL/min

• 1 mg/kg SC daily

Contraindications for enoxaparin

History of HIT

Active major bleed

Hypersensitivity to pork

Adverse Effects of Enoxaparin

Bleeding

Anemia

Thrombocytopenia

Hyperkalemia

Increased LFTs

Monitoring for Enoxaparin

Anti-Xa (only in pregnancy, obesity, or renal dysfunction)

Platelets

Hemoglobin

Hematocrit

SCr

Risk Factors for HIT

Source of heparin → UFH (bovine >> porcine) > LMWH

Duration of heparin exposure > 4 days

Past exposure → Within 30 days >> Within 100 days

Gender → Female > Male

Complications of HIT

Thrombocytopenia (low platelets)

Venous thrombosis

Arterial thrombosis

Limb gangrene

Skin lesions/necrosis

Disseminated intravascular coagulation (DIC) → clots AND bleeding

Death

A 4T score of 3 or lower indicates _____

Low probability for HIT

A 4T score of 4 or 5 indicates _____

Intermediate probability of HIT

A 4T score of 6 or higher indicates _____

High probability of HIT

Accuracy of 4T score

Good negative predictive measure, bad positive predictive measure

• 3 or lower → likely not HIT

• 4-5 or 6+ → need further testing (ELISA)

HIT Lab Tests

Enzyme-linked immunosorbent assay (ELISA)

Serotonin release assay (SRA)

Heparin-induced platelet aggregation (HIPA)

Enzyme-Linked Immunosorbent Assay (ELISA)

Detects PF4 in serum sample

High sensitivity, low specificity

• If negative → likely not HIT

• If positive → need another test (SRA)

Serotonin Release Assay (SRA)

Measures platelet activation by detecting the release of serotonin from test platelets

Takes 1-2 days for results

Gold standard, expensive

High sensitivity and specificity

Heparin-Induced Platelet Aggregation (HIPA)

Measures platelet aggregation of healthy and suspected patients in presence and absence of low-dose heparin

High specificity, low sensitivity

HIT Treatment

Stop all forms of heparin and LMWH, including flushes and prophylaxis

Argatroban is recommended

• If urgent cardiac surgery or PCI is required, bivalirudin is preferred

Warfarin is the only oral anticoagulant indicated (fondaparinux and DOACs are off-label)

• Do not start until platelets are at least 150000/mm³

• Overlap with a non-heparin anticoagulant for a minimum of 5 days and until the INR is within target range for 24 hours

  • Argatroban falsely elevates the INR

Starting warfarin too soon in treatment of HIT may induce _____

Limb gangrene and necrosis

Duration of HIT treatment

For patients with HIT and thrombosis (HITT) → 3 months

For patients with HIT and no thrombosis → 1 month

Administration of Argatroban for Treatment of HIT

IV infusion

Decrease dose in hepatic impairment

Contraindication for Argatroban/Bivalirudin

Active major bleeding

Adverse Effects of Argatroban/Bivalirudin

Bleeding

Anemia

Hematoma → large collection of blood

Monitoring for Argatroban

aPTT

Platelets

Hemoglobin

Hematocrit

Liver function

Administration of Bivalirudin for Treatment of HIT

IV infusion

Decrease dose when CrCl < 30 mL/min

Monitoring for Bivalirudin

ACT (activated clotting time) → quick test

Platelets

Hemoglobin

Hematocrit

Renal function

Dosing of Apixaban for VTE Treatment

10 mg PO BID x 7 days, then 5 mg PO BID

Contraindications for Apixaban

Active pathological bleeding

Avoid use with strong dual inducers of CYP3A4 and P-gp

Adverse Effects of Apixaban/Rivaroxaban

Bleeding

Anemia

Monitoring for Apixaban/Rivaroxaban/Edoxaban

Hemoglobin

Hematocrit

SCr (renally eliminated)

LFTs (hepatically metabolized)

What is the only DOAC indicated for VTE propylaxis in acutely ill medical patients?

Rivaroxaban

Dosing of Rivaroxaban for VTE Treatment

15 mg PO BID x 21 days, then 20 mg PO daily

If CrCl < 30 mL/min → AVOID USE

The 15 mg and 20 mg strengths if rivaroxaban must be _____

Taken with food

Contraindications for Rivaroxaban

Active pathological bleeding

Avoid use with strong dual inducers/inhibitors of CYP3A4 and P-gp

Dosing of Edoxaban for VTE Treatment

60 mg PO daily (start after 5-10 days of parenteral anticoagulation)

If CrCl 15-50 mL/min OR ≤ 60 kg OR on certain P-gp inhibitors

• 30 mg daily

If CrCl < 15 → USE NOT RECOMMENDED

Contraindication for Edoxaban

Active pathological bleeding

Adverse Effects of Edoxaban

Bleeding

Anemia

Rash

Increased LFTs

Dosing of Fondaparinux for VTE Treatment

< 50 kg → 5 mg SC daily

50-100 kg → 7.5 mg SC daily

> 100 kg → 10 mg SC daily

If CrCl 30-50 mL/min → USE CAUTION

If CrCl < 30 mL/min → CONTRAINDICATED

Contraindications for Fondaparinux

Active major bleed

CrCl < 30 mL/min

< 50 kg (prophylaxis)

Thrombocytopenia

Bacterial endocarditis

Adverse Effects of Fondaparinux

Bleeding

Anemia

Thrombocytopenia

Hypokalemia

Hypotension

Monitoring for Fondaparinux

Anti-Xa

Platelets

Hemoglobin

Hematocrit

SCr

Dosing of Dabigatran for VTE Treatment

150 mg PO BID (start after 5-10 days of parenteral anticoagulation)

If CrCl < 50 mL/min + P-gp inhibitor → AVOID USE

Contraindications for Dabigatran

Active pathological bleeding

Mechanical prosthetic heart valves

Adverse Effects of Dabigatran

Bleeding (more GI), dyspepsia, gastritis-like symptoms

Monitoring for Fondaparinux

Hemoglobin

Hematocrit

SCr

Important patient counseling for dabigatran

Must dispense in original package, patient should keep in in this bottle

• Prone to moisture → loss of potency

Take with food to minimize GI side effects

Swallow capsule whole → do NOT open

• If opened → increased absorption → increased risk of bleeding

Take with a full glass of water

Dosing of warfarin for VTE treatment

10 mg daily for first 2 days, then adjust dose per INR values in healthy outpatients

• Start with lower doses (≤5 mg) for elderly, malnourished, liver disease, heart failure, high risk of bleeding, or drug-drug interactions

• With acute DVT/PE, start warfarin on the same day as parenteral anticoagulant and continue both for a minimum of 5 days until the INR is 2-3 for at least 24 hours

Contraindications for warfarin

Pregnancy (except with mechanical heart valves)

Malignant hypertension (VERY high BP)

Hemorrhagic tendencies

Eye or CNS surgery

Adverse Effects of Warfarin

Bleeding

Skin necrosis

Purple toe syndrome

• Rare, usually if INR is not within goal

Monitoring for Warfarin

INR

Hemoglobin

Hematocrit

Drug-drug Interactions with Warfarin

Increased bleed risk → NSAIDs, antithrombotic agents, garlic, ginger, ginkgo, ginseng, glucosamine, alcohol

Decreased effectiveness → alfalfa, green tea, coenzyme Q10, and St. John’s wort

Msjor substrate of CYP2C9 → inducers can decrease INR and inhibitors can increase INR

Converting from warfarin to a DOAC

Stop warfarin and convert to:

• Rivaroxaban for INR < 3

• Edoxaban for INR ≤ 2.5

• Apixaban for INR < 2

• Dabigatran for INR < 2

Converting from a DOAC to warfarin

Start parenteral anticoagulant and warfarin at the next scheduled dose of the DOAC

Activated partial thromboplastin time (aPTT)

Time to generate fibrin from the start of the intrinsic pathway

Anti-Factor Xa (Anti-Xa)

Looks only at the functional activity of heparin

More consistent and reliable results, expensive

Activated clotting time (ACT)

Preferred in cath lab due to shorter time for result and smaller blood sample required

International normalized ration (INR)

Patient PT/Control PT

Monitor effects of warfarin

How is the dose of warfarin adjusted in outpatient situation?

5-20% adjustments in the weekly dose

What is the preferred treatment for patients with VTE and without cancer?

DOAC > Warfarin > LMWH

What is the preferred treatment for patients with VTE and with cancer?

DOAC > LMWH

• Apixaban or LMWH preferred in patients with gastrointestinal malignancies

Warfarin is NOT used

Duration of Therapy for VTE Prophylaxis

Give throughout period of increased VTE risk, then stop

General surgical procedures → once ambulating regularly and other risk factors are gone, can discontinue

15-42 days following total knee or hip replacement surgery

What defines a provoked VTE?

Identifiable cause of the VTE (immobility, surgery, hypercoagulability)

Duration of Therapy for VTE Treatment

Provoked → 3 months

Unprovoked → At least 3 months (if low-moderate bleed risk)

Thrombolytic Therapy in VTE

Anticoagulation alone is preferred for acute leg or upper extremity DVT and for PE without hypotension

System throbolytic therapy is recommended for patients with acute PE associated with hypotension who do not have a high bleeding risk

Catheter-directed thrombolysis is recommended for acute PE associated with hypotension and a high bleeding risk, failed systemic thrombolysis, or shock that is likely to lead to death before systemic thrombolysis can take effect