Page 2220 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 132 Thrombocytopenia Caused by Platelet Destruction, Hypersplenism, or Hemodilution 1967

these patients tend to be less responsive to plasma exchange than routine blood testing. The cause of the mild reduction in platelet
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those with idiopathic TTP. count (approximately 75 × 10 /L to 150 × 10 /L) is believed to
represent a leftward shift in the normal platelet count range during
pregnancy related to one or more of hemodilution, reduced platelet
Drug-Induced Disseminated Intravascular Coagulation production, or increased platelet turnover. This condition is benign
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and is not associated with an increased risk for maternal bleeding or
On rare occasions, quinine causes severe thrombocytopenia accom- neonatal thrombocytopenia. Accordingly, no special maneuvers are
panied by marked coagulation abnormalities indicative of DIC. This indicated in these women, and the route of delivery should be
syndrome overlaps that of quinine-induced thrombotic microangi- determined by obstetric indications. Epidural anesthesia is believed
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opathy, and the explanation for the prominent coagulopathy is to be safe if the platelet count is at least 75 × 10 /L.
unknown. Although all patients with HIT have biochemical evidence
of increased thrombin generation, only about 10% to 20% have overt
DIC; however, these patients often present with large and small vessel Preeclampsia and Eclampsia
thrombosis.
Preeclampsia is characterized by the onset of hypertension and pro-
teinuria during pregnancy, especially in a primigravida near term.
Nonidiosyncratic Drug-Induced Thrombocytopenia Preeclampsia complicates approximately 5% of pregnancies, and the
frequency is higher in black women. Thrombocytopenia occurs in up
Most antineoplastic drugs produce dose-dependent pancytopenia to 50% of preeclamptic patients, and its severity generally parallels
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because of their effect on hematopoietic cells, including megakaryo- that of the underlying preeclampsia. A subset of patients with
cytes and their progenitor cells. Typically, the platelet count nadir preeclampsia has microangiopathic hemolysis, elevated liver enzymes,
occurs at a predictable time after treatment, and the count then and low platelets, widely known as the HELLP syndrome. This
quickly recovers. Unexpectedly severe or prolonged thrombocytope- condition usually indicates severe preeclampsia and is associated with
nia in patients receiving chemotherapy should suggest alternate a higher risk of fetal and maternal complications, including maternal
explanations (e.g., idiosyncratic thrombocytopenia caused by another hepatic rupture. Repeated clinical and laboratory assessment of these
drug). patients is important because this syndrome can mimic other life-
Mild to moderate thrombocytopenia develops in approximately threatening complications of pregnancy, such as overt DIC, TTP,
20% of patients who take valproic acid (an antiepileptic agent); septicemia, and acute fatty liver of pregnancy.
bleeding symptoms are uncommon. The mechanism of thrombocy- Increased platelet destruction is the mechanism for the thrombo-
topenia in this setting is unknown, but the condition appears to be cytopenia in preeclampsia. However, activation of the coagulation
nonidiosyncratic because the risk of thrombocytopenia correlates system is relatively modest, suggesting that thrombin generation may
strongly with serum concentrations of valproic acid metabolite. not be a major driver of the thrombocytopenia. Endothelial dysfunc-
Amrinone is another agent that can cause mild, dose-dependent tion (e.g., impaired nitric oxide synthesis) is a potential explanation
thrombocytopenia. for increased platelet turnover in preeclampsia.
Pharmacologic control of hypertension and rapid delivery are the
treatments for preeclampsia and usually result in resolution of the
Rapid Nonimmune Drug-Induced Thrombocytopenia thrombocytopenia within a few days. If delivery is not an option,
treatment with bed rest and aggressive antihypertensive therapy has
Some drugs produce rapid but generally mild and transient drops in been reported to result in an improved platelet count. However, the
the platelet count. These drugs include heparin, protamine, bleomy- clinical course is markedly variable, and some patients develop life-
cin, hematin, desmopressin (particularly in patients with type 2B von threatening organ failure. Plasmapheresis has been used in some
Willebrand disease), and porcine factor VIII. The mechanisms for patients, especially if there is evidence of thrombotic microangiopathy
thrombocytopenia in these syndromes are obscure. and organ dysfunction. Plasma exchange is appropriate for patients
whose clinical picture has features suggesting TTP.
Drug Hypersensitivity Reactions
Infection
Mild to moderate thrombocytopenia is sometimes observed in
patients with systemic drug hypersensitivity reactions. Co-morbid Infection is a common cause of thrombocytopenia, occurring in
clinical features can include generalized rash, fever, cholestasis, and approximately 50% to 75% of patients with bacteremia or fungemia
leukopenia. Allopurinol, isoniazid, sulfasalazine, and phenothiazine and in almost all patients with septic shock or DIC. Even when
drugs, among others, have been implicated in these reactions. caused by bacteremia, the thrombocytopenia is generally mild to
moderate in severity and is usually not accompanied by significant
Thrombocytopenia Secondary to Biologic coagulation abnormalities or bleeding. The likelihood of laboratory
evidence for DIC increases as the platelet count falls below 50 ×
Response Modifiers 10 /L. The mechanisms for thrombocytopenia in septicemia in the
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absence of DIC are uncertain but could include chemokine-induced
Use of purified or recombinant biologic response modifiers such as macrophage ingestion of platelets (hemophagocytosis) and direct
interferon, interleukin-2, and certain colony-stimulating factors has activation of platelets by endogenous mediators of inflammation
resulted in severe, reversible thrombocytopenia in some patients. (e.g., platelet-activating factor) or certain microbial products. In rare
Antilymphocyte globulins can also produce severe thrombocytopenia. situations, platelet-reactive autoantibodies are implicated. Various
explanations for thrombocytopenia in different types of infection are
listed in Table 132.6.
OTHER CAUSES OF DESTRUCTIVE THROMBOCYTOPENIA Unexplained thrombocytopenia in a hospitalized patient warrants
studies to exclude infection, such as blood cultures. Prompt recogni-
Incidental Thrombocytopenia of Pregnancy tion and treatment of the infection constitute the most important
therapy because platelet count recovery tends to parallel the resolu-
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Maternal thrombocytopenia occurs in 4% to 8% of pregnancies. tion of the infection. Prophylactic platelet transfusions are generally
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Most affected women are healthy and have no history of thrombo- not required unless the platelet count falls below 10 × 10 /L or
cytopenia, and their thrombocytopenia is incidentally detected by comorbid clinical features increase the likelihood of serious bleeding