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46 Part I: Clinical Evaluation of the Patient Chapter 4: Consultative Hematology 47

One should begin the evaluation of a new DVT by defining the AC. Both agents are oral, require adequate renal function, and produce a
context of the event. Critical questions include: reliable anticoagulant effect that need not be monitored or titrated. They
lack reliable antidotes in the event of bleeding, although such products
1. Were there any risk factors, such as surgery, immobility, trauma,
indwelling catheters, cirrhosis, nephrotic syndrome, inflammatory are in development. It should be noted that patients with poor warfa-
disorders, or systemic estrogen therapy (Chap. 133)? rin compliance are equally poor candidates for these agents. Because of
2. If present, are those risk factors modifiable and might they have rea- their short half-life, skipped doses will result in a prompt loss of AC and
sonably provoked the event? increased risk of recurrent thrombosis.
3. If dealing with a reoccurrence while on AC, had the patient been In general, there is insufficient information regarding the superi-
compliant with therapy? ority of one anticoagulant over another. There is abundant experience
4. Are there historical or physical clues that might suggest malignancy, with warfarin (Coumadin) and LMWH. The latter is often preferred in
APS, or a hereditary thrombophilia? patients with malignancy, although high-quality evidence in its support
is lacking. Dabigatran and rivaroxaban lack specific data in hereditary
When probing hard enough, one is often able to identify a “risk thrombophilias, malignancy, and APS, and therefore caution should be
factor” for thrombosis. This alone is insufficient to label an event “pro- exercised in these settings. Dabigatran showed an excess risk of bleeding
voked”; rather, that risk factor must be thought to have reasonably and thrombosis when compared to Coumadin in patients with mechan-
caused the event. Attribution of causality is arduous and ultimately ical heart valves, exemplifying the potential peril in assuming anticoag-
subjective. ulants are of equal efficacy in different settings.
When dealing with recurrent events in patients on AC, compliance Decisions regarding AC touch upon every aspect of a patient’s
must be probed at length. Labeling a patient as having “failed” therapy life and are not taken lightly. They are not as black and white as stan-
has significant consequences. First, this might suggest an underlying dardized chemotherapy regimens and require an understanding of the
thrombophilia, such as malignancy or APS. Second, the lack of clear patient’s lifestyle, values, and risk of recurrence. Such assessment is
superiority data of one agent over another makes management deci- difficult in the modern time-constrained environment. Furthermore,
sions murky. such decisions should not be made in a single-instance and then fol-
The physical exam must of necessity focus on the affected extrem- lowed indefinitely. Rather, the decision to continue (or withdraw) AC is
ity. However, a comprehensive exam may provide valuable clues. Ade- dynamic and should be revisited serially depending on the tolerance of
nopathy or temporal wasting might suggest malignancy. Arthritis and therapy and other medical comorbidities.
malar rash might suggest an autoimmune diathesis such as lupus.
Organomegaly and erythromelalgia should trigger concern for an MPN ARTERIAL THROMBOSIS
such as PV or ET. Spontaneous upper-extremity events might suggest
thoracic outlet syndrome whereas unprovoked left iliofemoral DVT, Consultation is often requested in patients with arterial thrombo-
particularly in young women, may represent May-Thurner syndrome. sis, such as myocardial infarction, cerebrovascular accident, or acute
Screening for underlying hereditary thrombophilias is often pur- limb ischemia. In the vast majority of cases, however, this is related to
sued although the general utility of this approach is not clear. This is underlying atherosclerosis with local inflammation rather than a pri-
discussed at length in Chap. 130. In general, such screening rarely mary hypercoagulable state. Risk factors, mechanisms, and treatment of
changes management and has the potential for error if performed at atherothrombosis are discussed in Chap. 134.
the incorrect time. For example, levels of antithrombin III, protein C, In rare cases where underlying risk factors for atherothrombosis
and protein S may be falsely low in the acute setting. Functional protein are absent or there is a strong family history of thrombosis, particu-
S levels might be reduced when the factor V Leiden mutation is pres- larly at young ages, we perform a limited hypercoagulable evaluation,
ent, leading to erroneous diagnosis. Anticardiolipin antibodies require including studies for the APS. Paroxysmal nocturnal hemoglobinuria
sustained elevation over 12 weeks to satisfy criteria for APS. Pregnancy (PNH) and MPNs may rarely result in arterial thromboses. We rarely
and hepatic disease can also affect the serum levels of various pro- and find it helpful to obtain studies for protein C, protein S, or antithrombin
anticoagulants and confound diagnosis. III deficiency, and do not obtain studies for factor V Leiden or proth-
The decision regarding the duration of therapy is complex (Chap. rombin 20210A mutations as these do not have a meaningful effect
133). These decisions must incorporate the risk of recurrence, risk of on management. Furthermore, routine screening for the thermolabile
bleeding, and patient preferences. Generally, patients with either a pro- variant of the methylenetetrahydrofolate reductase (MTHFR) should
voked or distal DVT may be treated for a finite course, generally three be discouraged as there is no evidence of benefit in reducing plasma
months. Patients with unprovoked DVT/pulmonary embolism (PE), homocysteine levels.
APS, recurrent thromboses, or active malignancy are often considered Hence, broad hypercoagulable evaluations are not useful in iso-
for indefinite therapy should the bleeding risk be acceptable. lated arterial thrombosis, as most findings are likely incidental rather
In patients with unprovoked events who discontinue AC after than causal, and do not have a direct impact on patient management.
a finite course, efforts aimed at risk stratification via D-dimer assays
appear to be useful. Thromboprophylaxis with aspirin, has shown IMMATURE CELLS ON THE BLOOD FILM
promise. However these approaches are not standardized. The Amer-
ican College of Chest Physicians publishes evidence-based antithrom- Consultations may arise from the discovery of incidental abnormali-
botic guidelines that provide specific recommendations for a variety of ties on the blood film. Nucleated RBCs (nRBCs) and immature myeloid
scenarios and are a useful resource. cells are relatively common.
The availability of new, oral anticoagulants has dramatically
changed AC management from both the patient and physician perspec-
tives. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor NUCLEATED RED BLOOD CELLS
Xa inhibitor, are FDA approved for the treatment of venous thrombo- The clinical lab may report the finding of nRBCs, which is often reported
embolism, with the former requiring an initial 5 to 10 days of parenteral in the differential as #nRBC/100 WBC.

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