Page 2208 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 132

THROMBOCYTOPENIA CAUSED BY PLATELET DESTRUCTION,

HYPERSPLENISM, OR HEMODILUTION

Theodore E. Warkentin

Thrombocytopenia is defined as a platelet count below the lower drug, recent infection); (3) the presence of symptoms of a secondary
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limit of the normal range (≈150 × 10 /L). Sometimes an expanded illness, such as a neoplasm, infection, or an autoimmune disorder
definition of thrombocytopenia is appropriate. For example, an such as systemic lupus erythematosus (SLE); (4) history of recent
abrupt drop in the platelet count can signify the onset of a platelet- medication use, alcohol ingestion, or transfusion; (5) presence of risk
destructive process such as heparin-induced thrombocytopenia (HIT) factors for certain infections, particularly human immunodeficiency
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or bacteremia even if the platelet count remains above 150 × 10 /L. virus (HIV) infection or viral hepatitis; and (6) family history of
This is especially relevant in the second or third week after surgery thrombocytopenia.
because patients usually have platelet counts that peak at levels 2–3 As part of the physical examination, evidence of hemostatic
times greater than their usual preoperative value (postoperative impairment should be sought, as well as secondary causes of throm-
thrombocytosis). bocytopenia. The signs of platelet-related bleeding include petechiae
In the clinical evaluation of a patient with thrombocytopenia, three and purpura. Petechiae typically occur in the dependent regions of
questions must be asked. First, could the patient have pseudothrom- the body or on traumatized areas. Spontaneous mucous membrane
bocytopenia? Second, what is the most likely explanation for the bleeding (wet purpura), epistaxis, and gastrointestinal bleeding
thrombocytopenia? And third, what are the risks posed by the caus- indicate a more serious hemostatic defect. Although petechiae are
ative disorder and the severity of the thrombocytopenia? For example, common in patients whose platelet counts are less than 10–20 ×
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severe thrombocytopenia caused by drug-dependent antibodies or 10 /L, most patients with platelet counts over 50 × 10 /L have no
platelet-reactive autoantibodies is often associated with bleeding. By signs of hemostatic impairment. The physical examination may
contrast, thrombocytopenia caused by HIT antibodies or attributable provide an explanation for the thrombocytopenia. For example,
to disseminated intravascular coagulation (DIC) secondary to adeno- enlarged lymph nodes may indicate a viral infection, such as infec-
carcinoma is associated with thrombosis. Often, the underlying cause tious mononucleosis or HIV infection, or a neoplastic process. An
of the thrombocytopenia (e.g., bacteremia, cancer, cirrhosis), rather enlarged spleen raises the possibility of hypersplenism.
than the thrombocytopenia itself, poses the greater risk.
Thrombocytopenia can be caused by any of four general mecha-
nisms: (1) platelet underproduction, (2) increased platelet destruction Timing of Onset and Severity of Thrombocytopenia
or consumption, (3) platelet sequestration, and (4) hemodilution.
Platelet underproduction usually occurs in association with under- Many thrombocytopenic disorders, particularly those involving an
production of other blood cell lines, which results in bicytopenia immune pathogenesis, exhibit characteristic temporal features that can
or pancytopenia. Thrombocytopenia caused by increased platelet aid in the diagnosis. For example, if the platelet count begins to fall
destruction develops when the rate of platelet loss surpasses the ability 5–10 days (median, 6–7 days) after starting a new drug or after a blood
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of the bone marrow (BM) to produce platelets and may be caused transfusion and reaches a nadir of less than 20 × 10 /L a few days later,
by immune or nonimmune mechanisms (Table 132.1). Thrombocy- the diagnosis of drug-induced immune thrombocytopenia (D-ITP) or
topenia from platelet sequestration is caused by redistribution of posttransfusion purpura (PTP), respectively, should be considered (Fig.
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platelets from the circulation into an enlarged splenic vascular bed. 132.2). Patients with these disorders typically have mucocutaneous
Hemodilution is characterized by a decrease in the number of plate- bleeding and are at risk for fatal intracranial hemorrhage.
lets, as well as red blood cells (RBCs) and white blood cells (WBCs) A similar temporal profile is also characteristic of typical-onset
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as a result of the administration of colloid, crystalloid, or platelet- HIT, although there the platelet count only falls below 20 × 10 /L
poor blood products. in only 10% of affected patients (see Fig. 132.2); in approximately
In the postoperative period, platelet count changes reflect several 80% of patients, the platelet count nadir ranges from 20–150 ×
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processes, including initial hemodilution (immediate platelet count 10 /L, and in the remainder, the platelet count nadir never falls below
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decrease) and increased platelet consumption (first 2–4 days), at which 150 × 10 /L despite a large reduction in the platelet count. When
point the platelet count begins to rise because of increased platelet the platelet count falls abruptly after drug administration, the pos-
production; when the platelet count reaches its postoperative peak— sibility of rapid-onset thrombocytopenia caused by preexisting drug-
usually about 14 days after surgery—platelet production decreases dependent antibodies should be considered, as is well described with
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somewhat, and the platelet count returns to baseline (Fig. 132.1). In HIT. Indeed, so-called rapid-onset HIT is the presenting feature of
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addition to usual mechanisms, the differential diagnosis of thrombo- this adverse drug reaction in 25% to 30% of cases. Rapid-onset
cytopenia in pregnancy includes some unique causes (Table 132.2). thrombocytopenia is also a feature of glycoprotein (GP) IIb/IIIa
antagonist-induced ITP.
Occasionally, thrombocytopenia worsens in the first few days after
APPROACH TO PATIENTS WITH THROMBOCYTOPENIA surgery; this can occur with multiorgan system failure (e.g., cardio-
genic or septic shock) (see Fig. 132.2). If the patient develops con-
History and Physical Examination comitant DIC and hypotension, there is high risk for ischemic limb
injury secondary to microvascular thrombosis (“symmetric peripheral
Certain information should be ascertained, including (1) the location gangrene”), especially if the patient has “shock liver” (ischemic hepa-
and severity of bleeding (if any); (2) the temporal profile of the titis), which is a risk factor for severe depletion of protein C, an
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hemostatic defect (acute, chronic, or relapsing), particularly the important endogenous anticoagulant. If the platelet count falls to
temporal relationship with potential proximate triggers (e.g., new very low levels and is accompanied by microangiopathic hemolysis,
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