National Epidemiology of Inpatient Venous Thromboembolism in Patients with Hematologic Malignancies in United States from 1993 to 2012

Background: Venous thromboembolism (VTE) is an important cause of morbidity and mortality in patients with hematologic malignancies (HMs). The national burden of inpatient VTE in patients with HMs is not known.

Methods: We used the National Inpatient Sample (NIS), one of the largest publicly-available inpatient dataset in United States (U.S.), which represents a 20% stratified random sample of discharges from all hospitals, excluding rehabilitation and long-term acute care hospitals. The NIS is drawn from all States participating in Healthcare Cost and Utilization Project, representing more than 95 percent of the U.S. population. Discharge weights are used to generate national estimates. Patients with HMs were identified using ICD9 codes published by NIS and VTE was defined by ICD9 codes 451 - 453 and 415.1. Annual rates of inpatient VTE were calculated from 1993 to 2012 by HM type. Multivariate odds of inpatient VTE was determined by logistic regression controlling for confounders (age, sex, Charlson co-morbidity index, metastasis, chemotherapy, transfusion of blood products, major operating room procedure, primary hypercoagulable state, disseminated intravascular coagulation, heparin induced thrombocytopenia and thrombosis, antiphospholipid syndrome, obesity and calendar year). The malignancies with non-specific designation (e.g. unspecified leukemia) or with less than 1000 patients (weighted number) were excluded from results.

Results: 8.42 million hospitalized patients (weighted number) with HMs were identified, and 335,240 had VTE (3.98%). In patients with HMs, rates of inpatient VTE increased from 2.59% to 5.22% between 1993 and 2012 (p<0.01). A detailed analysis of VTE rates for various HMs is presented in Table 1. The HMs with highest odds of inpatient VTE are peripheral T-cell lymphoma (PTCL), anaplastic large cell lymphoma (ALCL) and primary central nervous system (CNS) lymphoma (OR 1.56, 1.53, and 1.39, p<0.05) as compared to all other HM. Among leukemias, hairy cell leukemia had higher odds of VTE (OR 1.19, p<0.05). The HMs with the least odds of VTE were acute lymphoid leukemia, chronic monocytic leukemia and plasma cell leukemia (OR 0.65, 0.66 and 0.71, p<0.05). The HMs with the highest rates of VTE were PTCL, large cell lymphoma and ALCL (6.96%, 6.35% and 6.27%). The HMs with lowest rate of VTE were megakaryocytic leukemia, acute lymphoid leukemia and acute monocytic leukemia (1.42%, 2.04%, and 2.73%).

Conclusions: Our study provides national estimates of inpatient VTE in HM, which are increasing over the last 20 years. Certain HMs have higher rates and odds of VTE as compared to others. Identification of these differences provides valuable information for the use of prophylaxis in HM with high risk of VTE.

Table 1: Multivariate Odds and Rates of Inpatient Venous Thromboembolism in Patients with Hematologic Malignancies (Total weighted N = 8.42 million)

Hematologic malignancy	Inpatient VTE rate (%)	Adjusted OR (95% CI) of inpatient VTE compared to all other HM
Hodgkin's disease
Hodgkin's disease - lymphocyte rich	3.86	1.15 (0.82 - 1.61)
Hodgkin's disease - nodular sclerosing	4.04	1.3 (1.18 - 1.43)
Hodgkin's disease - mixed cellularity	4.02	1.22 (0.89 - 1.68)
Hodgkin's disease - lymphocyte depleted	3.88	1.14 (0.73 - 1.77)
Non-hodgkin's lymphoma
Nodular lymphoma	4.89	1.2 (1.13 - 1.28)
Mycosis fungoides	4.83	1.25 (1.16 - 1.35)
Sezary's disease	3.99	1.08 (0.72 - 1.62)
Peripheral t-cell lymphoma	6.96	1.56 (1.32 - 1.85)
Burkitt's lymphoma	3.44	1.05 (0.97 - 1.15)
Marginal zone lymphoma	5.57	1.07 (0.91 - 1.26)
Mantle cell lymphoma	4.91	1.03 (0.92 - 1.15)
Primary CNS lymphoma	6.18	1.39 (1.18 - 1.64)
Anaplastic large cell lymphoma	6.27	1.53 (1.21 - 1.94)
Large cell lymphoma	6.35	1.36 (1.22 - 1.51)
Sarcoma
Myeloid sarcoma	4.24	1.14 (0.9 - 1.44)
Myeloma and leukemia
Multiple myeloma	4.57	1.14 (1.1 - 1.18)
Plasma cell leukemia	2.85	0.71 (0.5 - 1)
Lymphoid leukemia - acute	2.04	0.65 (0.61 - 0.69)
Lymphoid leukemia - chronic	3.43	0.76 (0.73 - 0.78)
Myeloid leukemia - acute	3.71	0.97 (0.93 - 1)
Myeloid leukemia - chronic	2.93	0.72 (0.68 - 0.76)
Monocytic leukemia - acute	2.73	0.75 (0.59 - 0.96)
Monocytic leukemia - chronic	2.74	0.66 (0.44 - 0.98)
Erythrocytic leukemia - acute	2.95	0.81 (0.5 - 1.32)
Megakaryocytic leukemia	1.42	0.48 (0.23 - 1.02)
Hairy cell leukemia	4.72	1.19 (1.07 - 1.32)