Thrombosis Deep Vein Disease

DESCRIPTION

Development of single or multiple blood clots within the deep veins of the extremities or pelvis, usually accompanied by inflammation of the vessel wall. The major clinical consequence is embolization, usually to the lung, that is frequently life-threatening.

System(s) affected: Cardiovascular
Genetics: N/A
Incidence/Prevalence in USA: Common (approximately 2 million cases per year)
Predominant age: Usually over 40
Predominant sex: Female > Male (1.2:1)

SIGNS AND SYMPTOMS

Many cases are completely asymptomatic, diagnosed retrospectively after embolization
Limb pain (common)
Limb swelling (common)
Leg pain on dorsiflexion of the foot (Homan's sign; common)
Palpable tender cord in affected limb (uncommon)
Warmth of skin over area of thrombosis (uncommon)
Redness of skin over area of thrombosis (uncommon)
Fever (uncommon, except in septic thrombophlebitis)
Non-tender swelling of collateral superficial veins (uncommon)
Massive edema with cyanosis and ischemia (Phlegmasia cerulea dolens, rare)

CAUSES

Venous stasis
Injury to vessel wall
Abnormalities of coagulation

RISK FACTORS

Clinical risk factors:
- Trauma, especially long bone fractures or crush injuries
- Surgery, particularly hip and knee surgery
- Prolonged immobility
- Pregnancy, especially the puerperium
- Indwelling central venous catheters
- Estrogen use (risk is confined to current usage and is proportional to estrogen content)
- Extreme high altitude (> 14,000 feet)
Pathological risk factors:
- Carcinoma
- Deficiencies of protein C, protein S, antithrombin III, all endogenous anticoagulants
- Presence of anti-phospholipid antibodies (also known as lupus anticoagulant or anti-cardiolipin antibodies)
- Nephrotic syndrome
- Polycythemia vera
- Homocystinuria (rare)
- Campylobacter jejuni bacteremia (very rare)
- Mutation on Factor V conferring resistance to activated protein C (most common risk factor for idiopathic DVT)

LABORATORY

No specific laboratory test is available for DVT
Protein C, protein S, antithrombin III, and anti-phospholipid antibodies can be measured in some laboratories. However, as these are rare causes of DVT, they are not routinely indicated and should be ordered only when the clinical circumstances suggest such a disorder.

Drugs that may alter lab results:

Heparin, estrogens may lower antithrombin III levels
Coumadin affects protein C and protein S function, so may interfere with functional assays of these proteins

Disorders that may alter lab results:

Thrombosis itself lowers antithrombin III levels, so any workup for antithrombin III deficiency must be performed after the patient has completed therapy
Syphilis and systemic lupus erythematosus are associated with increased anti-phospholipid antibodies

PATHOLOGICAL FINDINGS

Clot consisting predominantly of red blood cells, with some platelets and fibrin attached to the vessel wall at one end, with proximal end floating free in the lumen. Varying degrees of inflammation of the vessel wall are present.
Biochemical abnormalities such as proteins S, C, or antithrombin III deficiency, anti-phospholipid antibody, or homocystinuria are found in only a small minority of cases
Mutant Factor V conferring resistance to protein C ("Factor V Leiden") is a common abnormality, but routine clinical tests for the mutation are not yet in widespread use

SPECIAL TESTS

N/A

IMAGING

Imaging studies are necessary to diagnose or rule out suspected DVT
Contrast venography is the gold standard test (i.e., most sensitive and specific). Disadvantages include discomfort, technical difficulty and small risk of morbidity.
B-mode ultrasound combined with Doppler flow detection (duplex ultrasound); noninvasive, highly sensitive and specific for popliteal and femoral thrombi. Disadvantages include poor ability to detect calf vein thrombi; it is a highly operator-dependent technique; and its inability to reliably distinguish extrinsic compression of the vein from intrinsic clot.
Impedance plethysmography (IPG); probably as accurate as duplex ultrasound, less operator dependency, but poor at detecting calf vein thrombi
125 I-fibrinogen scan; detects only active clot formation; very good at detecting ongoing calf thrombi. Major disadvantage is that it takes 4 hours for results. This test has generally been supplanted by duplex ultrasound and IPG.

DIAGNOSTIC PROCEDURES

N/A

APPROPRIATE HEALTH CARE

Patients with DVT confined to the calf (i.e., distal to the popliteal system) can be managed conservatively as outpatients. All others should be admitted.

GENERAL MEASURES

For hospitalized patient - intravenous anticoagulation, a brief period of bedrest, and close observation for embolic events

SURGICAL MEASURES

When anticoagulants and thrombolytics are contraindicated, filtering devices ("umbrellas") can he inserted into the vena cava to "trap" emboli before reaching the lungs. Very large clots can be surgically removed in certain circumstances.

ACTIVITY

Bedrest for 1-2 days, then gradual resumption of normal activity, with avoidance of prolonged immobility

DIET

No special diet

PATIENT EDUCATION

Advise women taking estrogen of the risks, and the common symptoms of thromboembolic disease
Discourage prolonged immobility

PREVENTION/AVOIDANCE

General preventive measures such as avoiding prolonged immobility and using low-estrogen birth control pills when possible
Surgical patients need active prophylaxis: Low dose subcutaneous heparin with dosage adjusted to slightly prolong the APTT, low dose Coumadin, enoxaparin (low molecular weight heparin) and intermittent mechanical compression of the legs have all been effective in reducing the risks of DVT following various types of surgery.

POSSIBLE COMPLICATIONS

Pulmonary embolism (fatal in 10-20% of cases)
Systemic embolism ("paradoxical embolization") in cases where there is arteriovenous shunting (rare)
Chronic venous insufficiency
Post-phlebitic syndrome, i.e., pain and swelling in affected limb without new clot formation
Treatment-induced hemorrhage
Soft tissue ischemia associated with massive clot and very high venous pressures - phlegmasia cerulea dolens (very rare but should be considered a surgical emergency)

EXPECTED COURSE AND PROGNOSIS

About 20% of untreated proximal (i.e., above the calf) DVTs progress to pulmonary emboli, and 10-20% of those are fatal. With aggressive anticoagulant therapy, the mortality is decreased five- to tenfold.
DVT confined to the calf virtually never causes clinically significant emboli so does not require anticoagulation. However calf DVT's do sometimes propagate into the proximal system so known or suspected calf DVT's should be followed with IPG or duplex ultrasound every 3-5 days for 10 days and treated aggressively if they propagate into the popliteal or femoral system.

ASSOCIATED CONDITIONS

Budd-Chiari syndrome (hepatic vein thrombosis)
Renal vein thrombosis
Homocystinuria
Anti-phospholipid antibody syndrome

AGE-RELATED FACTORS

Pediatric: In this age group patients with DVT, in absence of preceding trauma, should be worked up for congenital coagulopathy
Geriatric: More common because predisposing conditions are more common
Others: N/A

PREGNANCY

Warfarin (Coumadin) is a known teratogen, so is contraindicated in pregnancy. Treat pregnant women with DVT with full-dose heparin initially, followed by subcutaneous heparin starting at 15,000 units twice daily with target APTT of 1.5–2 × control value.
Septic thrombophlebitis, usually associated with childbirth, requires antibiotic therapy as well as anticoagulation

OTHER NOTES

Home treatment of DVT with low molecular weight heparin (e.g., enoxaparin) may be appropriate for selected low risk patients

ABBREVIATIONS

DVT = deep vein thrombophlebitis
IPG = impedance plethysmography
INR = international normalized ratio

Clinical Investigations

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