Of the 100 patients identified with platelet counts <100 ×109/L, 27 patients were excluded for the following reasons: thrombocytopenia did not persist for >3 months (6), no outpatient records existed (10), interferon-related (4), chemotherapy or malignancy-related (3), and age <18 years (4); this left 73 evaluable cases for whom 73 matched controls were generated.
Of the case patients, nadir platelet count was ≤50 ×109/L in 58%, ≤30 ×109/L in 38%, and ≤10 ×109/L in 7%. The thrombocytopenia prevalence amongst 2298 outpatients who had CBC testing during the period from which the cases were obtained (May 2004-July 2005) was calculated at 3.2% (95% CI 2.5-4.0%). Of the 73 patients identified as thrombocytopenia cases, 43 (59%) were classified as incident cases of thrombocytopenia (platelet count was normal on preceding CBCs at our clinic) while 30 cases (41%) were defined as preexisting (prevalent) cases in which thrombocytopenia existed at the time of initial presentation to our clinic. Thrombocytopenia had not resolved at the time of last labs in 64% of cases. In these cases, the median duration of thrombocytopenia was 3.3 years (Interquartile range (IQR)=1.2-6.5 years), while it was 2.0 years (IQR=1.1-3.5) in cases with resolution of thrombocytopenia.
The shows demographic characteristics of cases and controls at the time of onset of thrombocytopenia as well as the characteristics associated with thrombocytopenia on univariate analysis and multivariate analysis. HIV RNA detectability, HCV infection, and cirrhosis remained significantly associated with thrombocytopenia status after adjusting for the other model variables. In fact, 98% of case patients compared to 53% of controls had at least one of these risk factors, and all three were observed in 15% of cases compared to none of the controls. In patients without HCV infection or cirrhosis, detectable HIV RNA was strongly associated with thrombocytopenia case status (present in 21 of 22 cases versus 5 of 22 of controls with available HIV RNA data, OR =17.5 (CI 2.3-127.4) p=.006). In contrast, in patients with known HCV infection or cirrhosis, HIV RNA detectability did not differ significantly between cases and controls.
Univariate & Multivariate Analysis of Characteristics and Laboratory Values from Cases of Thrombocytopenia and Matched Controls
Major bleeding events defined as gastrointestinal, intracranial, or events requiring hospitalization occurred in 13 cases compared to 2 controls (OR 6.5, CI 1.5-28.8; P= 0.014). Amongst case patients, major bleeding events were not associated with nadir platelet count or duration of thrombocytopenia; however, there was an association with cirrhosis (OR = 11.5, CI 2.3-58.0, P=0.003) and a trend toward an association with HCV infection (OR = 3.92, CI 0.8-19.3, P=0.09). Compared to controls, cases with thrombocytopenia were more likely to suffer death from any cause or major bleeding events during their history of thrombocytopenia; however no fatal bleeding events occurred. Nine deaths occurred amongst cases compared to 0 in control subjects (P=0.002, chi-squared); control subjects, however, were more likely to have unknown vital status (7 cases vs. 16 controls, P=0.04, chi-squared).
Nineteen case patients (26%) were treated for thrombocytopenia with 7 documented as receiving >1 type of treatment. Treatments included: corticosteroids (received by 11 patients); platelet transfusions, IVIG, and anti-D (each received by 5); progesterone (3); splenectomy (2); and vincristine (1). In addition, 5 patients required packed red cell transfusion due to a major bleeding event.