Venous thromboembolism
Definitions:
VTE refers to the presence of DVT or PE.
Calf-vein thrombosis less likely significant VTE, 80% resolve spontaneously
Proximal deep venous thrombosis (DVT) of popliteal, femoral (including superficial femoral vein) or iliac veins.
PE originating from DVT accounts for ~600,000 case every year.
Classification: The anatomic location of DVT, PE, clot burden, and sequelae may affect prognosis and treatment recommendations.
Deep or superficial
Proximal or distal
Femoral vein replaced the term superficial femoral vein.
Proximal LE DVTs occur in or superior to the popliteal vein (or the confluence of tibial and peroneal veins), whereas distal DVTs occur more inferiorly.
Location in the pulmonary arterial system characterizes PEs as central (main pulmonary artery, lobal, or segmental) or distal.
Risk Factors
Virchow's triad: stasis, endothelial injury, and hypercoagulability states.
Age >40 years (increase with advanced age)
Previous history of VTE (DVT or PE) at a young age <50 years.
Trauma to symptomatic leg within 60 days.
Prolonged immobilization (major surgery, stroke, paralysis, travel) in the past 4 weeks, but bed rest of >3 days can do it. Major surgery within past 4 weeks.
Family history of DVT in 1° relatives.
Thrombosis in unusual anatomic locations
Spontaneous (idiopathic) thrombosis, despite absence of an inherited thrombophilia and detectable autoantibodies, predispose patients to future thromboses.
Recurrent fetal loss.
Obesity
Pregnancy
CHF
Nephrotic syndrome
Thrombophilias: ATIII def, dysfibrinogenemia, APA syndrome, dysfibrinogenemia, factor V Leiden mutation, Factor XII def, hyperhomocysteinemia, plasminogen def, protein C def, protein S def, prothrombin 20210A mutation.
Homocystinuria caused by deficiency of cystathione-beta-synthase causes extremely high plasma homocysteine and arterial and venous thromboembolic events beginning in childhood.
Malignancy
Meds: Estrogen use, HRT, tamoxifen, raloxifene
UC & Crohn dz, Bechet syn
DIC, HIT
PNH or myeloproliferative d/o manifest as unusual spontaneous venous thromboses, such as cavernous sinus thrombosis, mesenteric vein thrombosis, or portal vein thrombosis.
TTP-HUS
At least 10% of patients with SLE have evidence of LA; however, most patients with LAs do not have SLE.
Both HIT and APA syndrome can cause arterial or venous thrombi.
Other causes of pulmonary arterial occlusion include insitu thrombi (sickle cell, marrow fat embolism, amniotic fluid embolism, pulmonary artery sarcoma, and fibrosing mediastinitis)
Clinical features
DVT manifests as calf pain, swelling, pain on dorsiflexion (Homan's sign) - don't try to elicit it, no symptoms, mottled apperance, may appear like cellulitis or gout flare up.
Lower extremity swelling >3 cm compared with unaffected side, edema, erythema, warmth, tenderness, palpable cord, Homan's sign positive.
PE manifest as tachycardia, dyspnea, hypoxia, pleuritic chest pain, cough, wheezing, syncope, hypotension, hemoptysis, new right sided heart failure, and PEA.
Tachypnea, crackles, tachycardia, fever, cyanosis, pleural friction rub, loud P2, JVD, right sided S3, Graham's Steele's murmur (PR)
As long as this superficial venous system, which has connections with the deep venous system, remains patent, none of the classic clinical features of DVT will occur, because blood will drain from the unobstructed superficial system. The ABG is shows hypoxic, hypocapnia, alkalosis, in a widened alveolar-arterial gradient.
DDx:
DDx of unilateral LE swelling includes Baker cyst, hematoma, venous insufficiency, postphlebitic syndrome, lymphedema, sarcoma, arterial aneurysm, myositis, cellulitis, rupture of the medial head of the gastrocnemius, and abscess.
Symmetric bilateral LE edema: CHF, renal or liver failure rather than DVT.
Musculoskeletal and arteriovascular d/o in association with lower extremity pain.
DDx for PE: dissecting Aortic aneurysm, pneumonia, acute bronchitis, bronchocarcinoma, pericardial or pleural disease, heart failure, costochondritis, and MI.
Diagnostic studies:
Pretest probability of a DVT when combined with the results of compression US or a D-dimer test, or both, in determining to exclude or accept the diagnosis of DVT or perform additional imaging studies.
D-dimers. Pts with positive test require further testing. If clinical probability of DVT is low and/or a non-invasive test is negative, DVT can be excluded. Also can exculde PEs.
aPTT or PT/INR may be prolonged by the presence of LAs.
Lab eval of thrombophilic states
Inherited thrombophilias:
Prothrombin gene mutation: G20210A mutation
Protein C level/activity,
Free protein S level/protein S activity, Antithrombin heparin cofactor activity
Factor V Leiden (most common inherited hypercoagulable state): Activated protein C resistance, if positive factor V Leiden PCR confirmation
Hyperhomocysteinemia: fasting plasma homcysteine level
Acquired thrombophilias
APA synd: IgG and IgM cardiolipin abs, Lupus anticoag, IgG and IgM beta2-glycoprotein-1 antibodies.
PNH: RBC or WBC flow cytometry for loss of CD55, CD59, CD24
Myeloproliferative d/o: JAK-2 mutation.
Imaging
DVT-specific testing:
Non-invasive testing has low sensitivity in asymptomatic patients.
Initial dxtic test must be noninvasive, venous duplex U/S. It has low sensitivity to detect calf DVT, parts of the deep femoral vein, parts of the UE venous system, and hte pelvic veins. Also, the presence of old DVT may make noninavasive testing difficult to interpret. LE venous compression U/S is used in a patient with suspected PE when the V/Q scan or CT chest w/ contrast is inconclusive or negative, but PE is highly suspicious. Proximal DVT can serve as a surrogate for PE; if picked up on U/S, in patients who are highly suspicious of PE, and who have C/I to or difficulty completing imaging for PE.
Serial testing can improve diagnostic yield. If there is high clinical suspicion of LE DVT and the initial non-invasive test result is negative, one can withold anticoagulation and repeat testing at least once 3-14 days later.
Venography, the gold-standard technique for Dx DVT needs placement of IV catheter, administration of iodinated contrast, and exposure to radiation. Before doing this, do other non-invasive testing. Dye allergy and renal dysfunction, preclude iodinated contrast administration.
MR venography, and CT venography in conjunction with CT-thorax (spiral CT) with IV contrast may detect other pathologies including DVT and PE.
PE-specific testing
ECG: RAD, righ-sided strain pattern with characteristic S1Q3T3
Tropinin, D-dimer, BNP, ABGs, CXR may help determine the pretest probability.
If clinical probability is low, negative d-Dimer, PE is unlikely and does not need further evaluation.
Contrast enhanced spiral (helical) chest CT. Uses PE protocol that included IV administration of iodinated contrast and exposure to radiation. C/I in renal dysfunction and dye allergy.
Multidetector CT has better sensitivity than single-detector CT for evaluation of patients with suspected PE.
Spiral CT picks up proximal (large) PEs, but has lower sensitivity in picking up small (distal) emboli.
Sensitivty of CT for VTE improves if CT pulmonary angiography results and combined with high clinical suspicion, and proximal LE CT venography that assesses for DVT.
Clinical suspicion discordant with the objective test finding (e.g., high suspicion with a negative CT scan, or low suspicion with a positive CT scan) should lead to further testing.
V/Q scanning. Needs administration of radioactive material (IH and IV routes)
Classified as normal, nondiagnostic (i.e., very low probability, low probability, intermediate probability) or high probability for PE.
Most useful in a patient with normal CXR, because nondiagnostic V/Q scans occur in the setting of abnormal CXR.
High clinical suspicion improves accuracy of V/Q scanning. Patients with normal or high-probability V/Q scans and matching pretest clinical suspicion, have high likelihood of PE, positive predictive value of 96%.
MRA. MRI with administration of nonionic contrast agent (gadolinium). Sensitive test for dx of acute PE>
Pulmonary angiography. Gold standard. Needs placement of PA cath, infusion of IV contrast, and exposure to radiation.
Echocardiography is used to assess cardiopulmonary reserve and evidence of end-organ damage (RV dysfunction) in patients with PE. It has a role in determining the need for thrombolytic therapy.
Treatment
VTE therapy goals are to prevent recurrent VTE, sequelae of VTE (post-phlebitic syndrome where Pts has pain, edema, and ulceration), pulmonary HTN, and death. Also complications of therapy are avoided (bleeding and HIT)
Lab test: CBC, PT, and aPTT done before starting anticoagulation).
Initial Tx of VTE should consist of parenteral anticoagulation, either with IV or SC UFH, SC LMWH, or SC pentasaccharide (fondaparinux); unless C/I.
Possible exclusion criteria for pharm VTE prophylaxis:
active bleeding
hypersensitivity to UFH and LMWH
uncontrolled HTN
renal insuff (CrCl<30 ml/min)
coagulopathy
HIT
recent IO or IC surgery, spinal tap or epidural <12 h, surgical proc.
Medications:
Anticoagulants.
UFH comes from porcine intestinal mucosa. It catalyzes the inactivation of thrombin and factor Xa by anithrombin.
Short duration of action and easily reversible with protamine sulfate, thus, is the anticoagulant of choice for patients with increasing risk of bleeding.
Therapeutic anticoagulation. UFH given as IV bolus, followed by continuous infusion. Bolus 80 units/kg (rounded to nearest 100 units). F/up infusion, 18 units/kg/hr.
For Pts with STEMI, typical bolus is 60 units/kg (max: 5000 units), and infusion 12 units/kg/hr (max: 1000 units/hr).
UFH may be administered subcutaneously: initial dose of 333 units/kg, SC, followed by a fixed dose of 250 units/kg, q12hr.
Prophylactic dosing:
Heparin, 5000 units SC q8 - 12 hr or
LMWH (enoxaparin), 40 mg SC or 4000 units SC daily, or
Dalteparin, 5000 units SC daily,
Fondaparinux, 2.5 mg SC daily.
ASA alone is not adequate for DVT prophylaxis.
At-risk patients with c/i to anticoagulation prophylaxis should receive mechanical prophylaxis with intermittent pneumatic compression or graded compression stockings.
Pretest probability of deep vein thrombosis (Wells)
Clinical feature Score
Active cancer (treatment ongoing or within the previous 6 months or palliative) 1
Paralysis, paresis, or recent plaster immobilization of the lower extremities 1
Recently bedridden for more than 3 days or major surgery, within 4 weeks 1
Localized tenderness along the distribution of the deep venous system 1
Entire leg swollen 1
Calf swelling by more than 3 cm when compared to the asymptomatic leg (measured below tibial tuberosity) 1
Pitting edema (greater in the symptomatic leg) 1
Collateral superficial veins (nonvaricose) 1
Alternative diagnosis as likely or more likely than that of deep venous thrombosis -2
Score
High probability 3 or greater
Moderate probability 1 or 2
Low probability 0 or less
Modification:
This clinical model has been modified to take one other clinical feature into account: a previously documented deep vein thrombosis (DVT) is given the score of 1. Using this modified scoring system, DVT is either likely or unlikely, as follows:
DVT likely 2 or greater
DVT unlikely 1 or less