Complicated Venous Thromboembolism or Comorbidities?
Key Points:
- Patients with complicated venous thromboembolism or certain comorbidities may require therapy that is different than patients with uncomplicated venous thromboembolism. The work group felt that these patients should be identified and treated individually rather than by a standard guideline.
- Complications or comorbidities of venous thromboembolism include massive PE, contraindications to anticoagulation, known history of heparin-induced thrombocytopenia (HIT), extensive iliofemoral thrombosis/phlegmasia, pregnancy, familial bleeding and clotting disorders, and severe renal dysfunction.
Massive PE
Patients who present with symptoms of PE associated with hemodynamic or respiratory compromise should be evaluated for massive PE. These patients may require treatment other than that discussed in the guideline.
Massive PE should be considered in the following circumstances: any hemodynamic instability, severe hypoxemia or respiratory distress, a V/Q or angiogram with 50% of the perfusion absent, an echocardiogram showing right heart strain or failure, an elevated pulmonary artery pressure, or a spiral CT suggesting severe occlusion. Massive PE has up to a tenfold greater mortality and treatment with thrombolytics appears to favorably affect the outcome. A recent study has also suggested that there may be some benefit for the use of thrombolytics in submassive PE. In this circumstance, specialty consultation and consideration of thrombolytics may be appropriate.
Patients with hemodynamic compromise may require immediate thrombolytic therapy. Normotensive PE patients with right ventricle (RV) dysfunction should be treated in-hospital (at least initially) where their vital signs can be closely monitored. Such patients should be considered for thrombectomy (either catheter-directed or open), thrombolysis, and/or inferior vena cava (IVC) filter placement if blood pressure support (i.e., pressors and augmentation of intravascular volume) is required, and possibly if hypoxemia cannot be corrected with supplemental oxygen therapy.
Evidence supporting this recommendation is of classes: A, B, D, M, R
Contraindications to Anticoagulation
Absolute contraindications would include patients who have active severe hemorrhage or recent intracranial hemorrhage. Relative contraindications include: recent or imminent surgery, trauma, anemia (hematocrit less than 30), renal disease, history of gastrointestinal hemorrhage, active peptic ulcer disease, and liver disease.
These patients require more intense monitoring for bleeding complications if given anticoagulation therapy. If not treated with anticoagulation therapy, serial ultrasounds for untreated calf DVT, or IVC filters for proximal DVT are indicated. (See Annotation #44, "Other Therapies.") Please refer to the NGC summary of ICSI's Antithrombotic Therapy Supplement for more information on contraindications to anticoagulation.
Evidence supporting this recommendation is of classes: A, B
Known History of Heparin-Induced Thrombocytopenia (HIT)
Thrombocytopenia can complicate heparin therapy. Both a non-immune and a more serious immune mediated platelet associated immunoglobulin G (IgG) reaction, HIT, have been described. If the patient has previously received heparin, especially within the past 3 months, thrombocytopenia may occur within hours or days.
Patients with HIT should not be treated with either unfractionated heparin (UFH) or low- molecular-weight heparin (LMWH). Direct thrombin inhibitors have been used successfully in this circumstance. (See Annotation # 44, "Other Therapies.") Please refer to the NGC summary of ICSI's Antithrombotic Therapy Supplement for more information on HIT.
Evidence supporting this recommendation is of class: C
Extensive Iliofemoral Thrombosis/Phlegmasia
Patients found to have extensive iliofemoral disease or evidence of phlegmasia will likely require inpatient monitoring and longer course of heparin/LMWH therapy than patients with uncomplicated DVT. Thrombolytic therapy may be of benefit in these patients for possible reduction of post-thrombotic complications. (See Annotation #44, "Other Therapies.")
Pregnancy
In pregnancy, warfarin is contraindicated because it crosses the placenta and is associated with embryopathy, central nervous system (CNS) abnormalities, and neonatal bleeding. Subcutaneous UFH, twice daily, has been the standard therapy in pregnancy. LMWH has shown no increased fetal complication, and was shown to have fewer bleeding complications than UFH.
Renal clearance of enoxaparin may be increased during pregnancy.
Anticoagulation will need to continue 4 to 6 weeks after delivery because the postpartum period is itself a high-risk time for thrombosis.
Please refer to the NGC summary of ICSI's Antithrombotic Therapy Supplement for more information on anticoagulation therapy during pregnancy.
Evidence supporting this recommendation is of classes: A, D, M
Familial Bleeding Disorders
Because of the complexity and controversy surrounding the use of standard anticoagulation to treat DVT in patients with familial bleeding disorders, these patients are excluded from the guideline. There is little data that has addressed the use of low-molecular-weight heparin in these patients. Although treatment for these patients may be similar to that found in the algorithm, the work group felt that these patients should be treated individually and not be included in the guideline.
Severe Renal Dysfunction (creatinine clearance less than 30 mL/minute)
These patients require closer monitoring for bleeding complications and dosing adjustments if LMWH is used. Patients with significant renal impairment (creatinine clearance less than 30 mL/min) can accumulate LMWH. The recommended doses in these patients are currently:
- Enoxaparin 1 mg/kg ONCE daily for therapeutic (treatment) doses. (Normal renal function dose is 1 mg/kg twice daily or 1.5 mg/kg once daily)
- Enoxaparin 30 mg ONCE daily for prophylactic doses. (Normal renal function dose is 30 mg twice daily or 40 mg once daily)
Please refer to the NGC summary of ICSI's Antithrombotic Therapy Supplement for more information on anticoagulation therapy in patients with renal dysfunction.
Evidence supporting this recommendation is of classes: B, C