Page 2342 - Hematology_ Basic Principles and Practice ( PDFDrive )

2084 Part XII Hemostasis and Thrombosis

Routine Investigations to Evaluate a Patient With Thrombosis
Test Abnormality Diagnostic Information
Complete blood Elevated hematocrit Myeloproliferative disorder (e.g., essential thrombocythemia, polycythemia
count Increased white count vera); may be found in paroxysmal nocturnal hemoglobinuria; if
Increased platelet count associated with heparin administration, consider heparin-induced
Leukopenia thrombocytopenia
Thrombocytopenia
Blood film Leukoerythroblastic changes Underlying neoplasm invading bone marrow
Liver function tests Abnormal tests May point to malignancy
Renal function Impaired renal function Assess prior to anticoagulation with heparin or low-molecular-weight heparin
or new oral anticoagulants
Urinalysis Proteinuria Nephrotic syndrome; may be associated with venous thromboembolism or
renal vein thrombosis
PT and aPTT Prolonged PT and aPTT To enable safe anticoagulation to proceed if required
Need to exclude lupus anticoagulant
aPTT, Activated partial thromboplastin time; PT, prothrombin time.

malignancy, or inherited deficiencies of antithrombin, protein C, or
protein S. These patients’ risk for recurrence is likely to be 15% at 1 CLINICAL EVALUATION OF PATIENTS WITH
year and up to 50% at 5 years. HYPERCOAGULABLE STATES

COMBINED INHERITED AND ACQUIRED A carefully taken history is essential to evaluate a patient with a
history of thrombosis. The patient’s age at the time of thrombosis,
HYPERCOAGULABLE STATES the location of the thrombosis, and results of objective diagnostic
tests should be recorded. A historical record of previous thromboses
Hyperhomocysteinemia is the prototypical hypercoagulable state and sites, and potential risk factors, such as recent surgery, trauma,
that occurs due to a combination of inherited and acquired factors. prolonged immobility, pregnancy, or estrogen use should be noted.
Homocysteine is an intermediate sulfur-containing amino acid that A family history of thrombosis, especially in first-degree relatives may
acts as a methyl group donor during the metabolism of methionine, point to a heritable thrombophilic defect; systemic symptoms, such
an essential amino acid derived from the diet. The interconversion as anorexia, weight loss, change in bowel habits, or gastrointestinal
of methionine and homocysteine depends on the availability of bleeding may suggest an underlying malignant condition.
5-methyltetrahydrofolate, a methyl group donor, vitamin B 12 and A full physical examination should be conducted with attention
folate, cofactors in the interconversion, and the enzyme methionine to abdominal or pelvic masses, lymphadenopathy, and skin changes
synthase. Increased levels of homocysteine can be the result of such as skin necrosis and livedo reticularis. Basic investigations are
increased production or reduced metabolism. Severe hyperhomocys- necessary to exclude acquired causes of thrombosis and to assess the
teinemia and cysteinuria are rare and are usually caused by deficiency patient’s general health and tolerance to anticoagulation (see box on
in the enzyme, cystathione β-synthetase. More common is mild to Routine Investigations to Evaluate a Patient With Thrombosis).
moderate hyperhomocysteinemia. This can be caused by genetic
mutations in methyltetrahydrofolate reductase (MTHFR) when
they are accompanied by nutritional deficiency of folate, vitamin THROMBOPHILIA SCREENING
B 12 , or vitamin B 6 . Common polymorphisms in MTHFR, C677T
and A1298C, are associated with reduced enzymatic activity and In the past, the indications for thrombophilia screening were some-
increased thermolability. The cofactor requirements are therefore what controversial, and the implications of such tests were often
increased with these mutations. Hyperhomocysteinemia also can be misinterpreted. It is now apparent that testing for heritable thrombo-
associated with certain drugs, such as methotrexate, theophylline, philia does not predict the likelihood of recurrence in unselected
cyclosporine, and most anticonvulsants, as well as some chronic patients with symptomatic venous thrombosis. For patients with a first
diseases, such as end-stage renal disease, severe hepatic dysfunction, episode of venous thromboembolism, thrombophilia screening is
and hypothyroidism. indicated only if the results influence the duration of treatment or
A fasting serum homocysteine level over 15 mmol/L is considered have an impact on family counselling regarding use of estrogen-
elevated. Although elevated levels were a common finding, routine containing compounds. It is reasonable to screen patients whose first
fortification of flour with folic acid has resulted in lower homocysteine episode of thrombosis occurred before the age of 40 years, patients
levels in the general population. Elevated serum levels of homocyste- with thrombosis in an unusual site, such as cerebral or mesenteric
ine have been associated with an increased risk for arterial thrombosis veins, and those with two or more first-degree relatives with unpro-
(myocardial infarction, stroke, and peripheral arterial disease) and voked thrombosis; retinal vein thrombosis is not an indication for such
venous thromboembolism. screening. Screening should not be done when patients are taking an
Elevated levels of homocysteine can be reduced by administra- anticoagulant. If indefinite anticoagulation therapy is planned, screen-
tion of folate with vitamin B 12 and vitamin B 6 . Randomized trials, ing is generally not required. Neonates and children with purpura
however, have shown that reduction of homocysteine levels with fulminans should be urgently tested for protein C or S deficiency, as
vitamin therapy does not reduce the risk for recurrent cardiovascular should adults who develop skin necrosis in association with vitamin
events in patients with coronary artery disease or stroke, nor does K antagonists (see box on When to Perform a Thrombophilia Screen).
it lower the risk for recurrent venous thromboembolism; whether
reduction of homocysteine levels is of benefit in peripheral artery
disease with bypass grafts is less certain. Nonetheless, based on LABORATORY EVALUATION OF THROMBOPHILIA
these negative trials and the declining incidence of hyperhomocys-
teinemia, the enthusiasm for screening for hyperhomocysteinemia Screening should include functional assays for antithrombin and
has waned. protein C, an immunoassay for free protein S, testing for activated