Hypercoagulable State


Hypercoagulable States

Clinical Features

Diagnostic Tests

Common Tests
CBC anemia; elevated packed cell volume (PCV); elevated WBC; elevated or reduced platelet count
Peripheral blood smear presence of red cell fragmentation, spherocytes, thrombocytopenia, pancytopenia, or macrocytes may suggest underlying pathology; presence of nucleated red blood cells, sickle-shaped cells, and Howell-Jolly bodies in sickle cell anemia
Activated PTT Reduced or prolonged
Fibrinogen fibrinogen is associated with prothrombotic state; reduced fibrinogen may indicate underlying DIC or dysfibrinogenemia
Prothrombin time prolonged
D-dimer normal or elevated
Serum albumin in nephrotic syndrome
Serum creatinine in nephrotic syndrome
Serum cholesterol in nephrotic syndrome
serum triglycerides in nephrotic syndrome
Thrombophilia test positive in inherited thrombophilia
Anti-thrombin III
PCR for factor V Leiden positive
lupus anticoagulant and anticardiolipin antibodies positive
homocysteine level elevated
factor VIII level elevated
Protein C
Protein S
PCR for JAK2 mutation Present
flow cytometry for paroxysmal nocturnal hemoglobinuria positive
heparin-induced thrombocytopenia test presence of antibodies
chest x-ray presence of lung nodules, pleural effusion, or mediastinal abnormality may suggest underlying occult malignancy
abdominal CT occult malignancy
Abdominal US occult malignancy
Tumor markers:
PSA, CEA, CA-125
detection of occult malignancy
24-hour urine collection for protein, or spot urine for protein/creatinine ratio Proteinuria in nephrotic syndrome
Emerging Tests
thrombin generation identification of prothrombotic phenotype
thromboelastography identification of prothrombotic phenotype


 

Treatment

Patient Group Tx Line Treatment
Non-Pregnant with a medical illness
No cancer:
Risk of VTE without excessive bleeding risk
1st low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux
  • The American College of Chest Physicians recommends that patients admitted to the hospital with an acute medical illness or into intensive care should have their risk of VTE assessed; if they have one or more additional risk factors they should receive thromboprophylaxis until discharge.
  • Patients who do not have a bleeding risk should receive pharmacologic prophylaxis.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
No cancer:
risk of VTE with excessive bleeding risk
1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients admitted to the hospital with an acute medical illness or into intensive care should have their risk of VTE assessed; if they have one or more additional risk factors they should receive thromboprophylaxis while in the hospital.
  • Patients with a high bleeding risk should receive mechanical methods of prophylaxis. These include graduated compression stockings and the use of intermittent pneumatic compression devices.
  • If used long term, these devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • Graduated compression stockings
    and/or
  • intermittent pneumatic compression device
with cancer:
ambulatory and on thalidomide or its derivatives
1st low molecular weight heparin (LMWH)
  • Thromboprophylaxis for ambulatory patients with cancer remains controversial and is not recommended.
  • However, the American Society of Clinical Oncology suggests that ambulatory patients with cancer who are receiving thalidomide or its derivatives may benefit from concomitant LMWH for duration of treatment with thalidomide (or derivative).
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.

Primary Options

  • enoxaparin
  • dalteparin
with cancer:
hospitalized without excessive bleeding risk
1st low molecular weight heparin (LMWH) or unfractionated heparin (UFH)
  • The American Society of Clinical Oncology recommends thromboprophylaxis (LMWH or UFH) during periods of hospitalization (up to 28 days post discharge).
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
with cancer:
hospitalized with excessive bleeding risk
1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis during periods of hospitalization (up to 28 days post discharge).
  • If used long term, devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
Non-Pregnant undergoing general surgery
moderate risk of VTE without excessive bleeding risk 1st low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux
  • Low-risk patients do not require thromboprophylaxis, as early and frequent mobilization is sufficient.
  • The American College of Chest Physicians recommends that patients undergoing general surgery at moderate risk of VTE should receive thromboprophylaxis. 
  • Patients without a bleeding risk should receive pharmacologic prophylaxis.
  • Therapy should be continued until discharge.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
moderate risk of VTE with excessive bleeding risk 1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk receive mechanical thromboprophylaxis.
  • If used long term, these devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.
  • Therapy should be continued until discharge.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
high risk of VTE without excessive bleeding risk 1st LMWH, unfractionated heparin (UFH), or fondaparinux,
-- AND --
Mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients at high risk of VTE without an excessive bleeding risk who are undergoing general surgery should receive both pharmacologic (LMWH, UFH, or fondaparinux) and mechanical thromboprophylaxis.
  • Therapy should be continued until discharge.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.

Primary Options

  • enoxaparin
    or
  • dalteparin
    or
  • heparin
    or
  • fondaparinux

    -- AND --
     
  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
high risk of VTE with excessive bleeding risk 1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis.
  • Therapy should be continued until discharge.
  • If used long term, devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
nonpregnant undergoing major gynecologic or urologic surgery
without excessive bleeding risk 1st LMWH or unfractionated heparin (UFH), and/or intermittent pneumatic compression
  • The American College of Chest Physicians recommends that patients undergoing gynecologic or urologic surgery should receive LMWH or UFH, and/or intermittent pneumatic compression, started just before surgery and used continuously while the patient is not ambulating.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.

Primary Options

  • enoxaparin
    or
  • dalteparin
    or
  • heparin
    -- AND/OR --
  • intermittent pneumatic compression device
with excessive bleeding risk 1st Mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis started just before surgery and used continuously while the patient is not ambulating.
  • If used long term, devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
nonpregnant undergoing orthopedic surgery
total hip or knee arthroplasty without excessive bleeding risk 1st LMWH, unfractionated heparin (UFH), fondaparinux, warfarin, rivaroxaban, or dabigatran
  • The American College of Chest Physicians recommends that patients undergoing total hip or knee arthroplasty should receive LMWH, UFH, fondaparinux, or warfarin with INR target of 2.5 and continued for 10 to 35 days after surgery.
  • LMWH should be started before surgery.
  • Fondaparinux should be given 6 to 8 hours after surgery or on the following day.
  • Warfarin should be given postoperatively.
  • Rivaroxaban should be given commencing 6 to 10 hours postoperatively, provided hemostasis is established.
  • Dabigatran should be initiated 1 to 4 hours postoperatively. A reduced-dose regimen is recommended for those with moderate renal impairment, those older than 75 years, and those on amiodarone. It is not recommended in patients with mechanical prosthetic heart valves.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
total hip or knee arthroplasty with excessive bleeding risk 1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis started just before surgery and continued for 10 to 35 days after surgery. [54]
  • If used long term, devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
hip fracture surgery without excessive bleeding risk 1st LMWH, unfractionated heparin (UFH), or fondaparinux, or warfarin
  • The American College of Chest Physicians recommends that patients undergoing hip fracture surgery should receive LMWH, UFH, fondaparinux, or warfarin with INR target of 2.5 continued for 10 to 35 days after surgery.
  • If a delay in surgery is anticipated, LMWH or UFH should be started preoperatively.
  • Fondaparinux should be started 6 to 8 hours after surgery or on the following day.
  • Warfarin should be given postoperatively.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
hip fracture surgery with excessive bleeding risk 1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis applied just before surgery and continued for 10 to 35 days after surgery.
  • If used long term, devices should be removed for only a short time each day, while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
spinal cord injury without excessive bleeding risk 1st LMWH or warfarin
  • The American College of Chest Physicians recommends that patients admitted with spinal cord injury should receive LMWH or warfarin with INR target of 2.5 throughout admission and during inpatient rehabilitation if mobility is impaired. 
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
spinal cord injury with excessive bleeding risk 1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis throughout admission and for duration of inpatient rehabilitation if mobility is impaired.
  • If used long term, devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
Non-pregnant with major trauma
without excessive bleeding risk 1st LMWH or warfarin
  • The American College of Chest Physicians recommends that patients admitted with major trauma should receive LMWH or warfarin with INR target of 2.5 throughout admission and during inpatient rehabilitation if mobility is impaired.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
with excessive bleeding risk 1st mechanical thromboprophylaxis
  • The American College of Chest Physicians recommends that patients with a high bleeding risk should receive mechanical thromboprophylaxis throughout admission and for duration of inpatient rehabilitation if mobility is impaired.
  • If used long term, devices should be removed for only a short time each day while the patient is mobilizing or bathing.
  • If the bleeding risk decreases, pharmacologic thromboprophylaxis should be considered.

Primary Options

  • graduated compression stockings
    and/or
  • intermittent pneumatic compression device
Pregnant
with antithrombin deficiency 1st LMWH or unfractionated heparin (UFH)
  • The American College of Chest Physicians recommend an individual risk assessment for asymptomatic pregnant women with heritable thrombophilia, with antepartum clinical surveillance or pharmacologic thromboprophylaxis (LMWH or UFH) and postpartum thromboprophylaxis for 4 to 6 weeks.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
with a heritable thrombophilia excluding antithrombin deficiency 1st clinical surveillance, or LMWH, or unfractionated heparin (UFH)
  • The American College of Chest Physicians recommends an individual risk assessment for asymptomatic women with other heritable thrombophilia, with antepartum clinical surveillance or pharmacologic thromboprophylaxis (LMWH or UFH) and postpartum thromboprophylaxis for 4 to 6 weeks.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
with antiphospholipid syndrome 1st LMWH, or unfractionated heparin (UFH), and aspirin
  • For women with antiphospholipid syndrome with hx of recurrent miscarriage or late pregnancy loss but no prior venous thromboembolism or arterial thrombosis, prophylactic LMWH or UFH in addition to aspirin is recommended throughout pregnancy.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
post cesarean section with one additional risk factor for VTE 1st low molecular weight heparin (LMWH), unfractionated heparin (UFH), or mechanical thromboprophylaxis
  • For women considered at low risk of VTE after cesarean section, early frequent mobilization is recommended without thromboprophylaxis.
  • For women considered at increased risk of VTE after cesarean section because of the presence of one risk factor in addition to pregnancy and cesarean section, the American College of Chest Physicians recommends pharmacologic thromboprophylaxis (LMWH or UFH) or mechanical prophylaxis while in the hospital following delivery.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.
post cesarean section with multiple risk factors for VTE 1st low molecular weight heparin (LMWH), or unfractionated heparin (UFH), and mechanical thromboprophylaxis
  • For women with multiple additional risk factors for thromboembolism who are undergoing cesarean section and are considered to be at high risk of VTE, the American College of Chest Physicians recommends that pharmacologic prophylaxis be combined with the use of graduated compression stockings and/or intermittent pneumatic compression while in the hospital following delivery.
  • Dose varies according to indication and institution; consult local specialist protocol for guidance on dose.