Disease burden, complication rates, and health-care costs of heparin-induced thrombocytopenia in the USA: a population-based study

Abstract

Background: Heparin-induced thrombocytopenia can be a life-threatening and limb-threatening complication of heparin therapy. Incidence and complication rates of this condition have been extrapolated from studies with modest sample sizes, and despite the availability of therapeutic interventions the outcomes of heparin-induced thrombocytopenia are not well understood. We aimed to estimate disease burden, complication rates, and costs of heparin-induced thrombocytopenia in the USA.

Methods: In this population-based study we analysed data from 2009 to 2013 from the Nationwide (National) Inpatient Sample (NIS), a large, all-payer inpatient health-care database in the USA. To validate the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for heparin-induced thrombocytopenia (289.84), we defined the sensitivity and specificity of this code using patient data from 2013 from a local hospital (Froedtert Memorial Lutheran Hospital, Milwaukee, WI, USA). The primary outcomes assessed were the incidence of hospital discharges with codes for heparin-induced thrombocytopenia and of discharges for heparin-induced thrombocytopenia associated with cardiopulmonary bypass, haemodialysis, hip or knee arthroplasty, trauma or injury (or both), and gingival or periodontal disease (or both). We also assessed the incidence of thrombosis, bleeding, limb or digit amputation, mortality, length of hospital stay, and associated hospital charges.

Findings: Between 2009 and 2013, 97 566 discharges from the NIS assigned the ICD-9-CM code for heparin-induced thrombocytopenia, and 149 911 247 discharges coded for non-heparin-induced thrombocytopenia, were analysed. Overall, heparin-induced thrombocytopenia was identified in 97 566 (0·065%; SE 0·0012) of 150 008 813 discharges, corresponding to approximately one in 1500 hospital admissions. Patients undergoing cardiopulmonary bypass had the highest rates of heparin-induced thrombocytopenia (7702 [0·63%; SE 0·03] of 1 230 362), followed by those undergoing haemodialysis (23 012 [0·47%; 0·01] of 4 908 100), those with gingival or periodontal disease, or both (106 [0·12%; 0·03] of 88 621), and those with trauma or injury, or both (541 [0·09%; 0·01] of 602 944); patients with hip (845 [0·04%; 0·004] of 1 943 353) and knee (676 [0·02%; 0·002] of 3 022 602) arthroplasty had the lowest rates of heparin-induced thrombocytopenia. Thrombosis (29 079 [29·8%; SE 0·4] of 97 566) and bleeding (6044 [6·2%; 0·2] of 97 566) were common complications in heparin-induced thrombocytopenia, and 1446 (23·9%; 1·2) of 6044 patients with heparin-induced thrombocytopenia who had haemorrhage died. 742 (0·76%; SE 0·06) of 97 566 patients with heparin-induced thrombocytopenia discharges underwent amputations compared with 173 043 (0·12%; 0·001) of 149 911 247 with non-heparin-induced thrombocytopenia discharges (adjusted odds ratio 5·095 [95% CI 4·309-6·023]; p<0·0001). Overall, in-hospital mortality was 9842 (10·1%; SE 0·2) of 97 508 in discharge summaries coded for heparin-induced thrombocytopenia compared with 3 206 700 (2·1%; 0·01) of 149 811 891 in discharges for non-heparin-induced thrombocytopenia (adjusted odds ratio 4·075 [95% CI 3·846-4·317]; p<0·0001). The median length of stay among live discharges was 8·9 days (IQR 4·6-17·1) and total hospital charges were US$83 072 (IQR 37 240-188 419) for heparin-induced thrombocytopenia discharges compared with 2·6 days (1·4-4·8) and $21 360 (11 426-41 917) for non-heparin-induced thrombocytopenia discharges (p<0·0001 for both). 333 discharges from a local hospital were analysed to assess the diagnostic sensitivity and specificity of the heparin-induced thrombocytopenia ICD-9-CM code; sensitivity was 90·9% (95% CI 57·1-99·5) and specificity was 94·4% (91·1-96·6).

Interpretation: Complication rates for heparin-induced thrombocytopenia remain high and more effective preventive and treatment interventions are needed.

Funding: None.

Figure 1.. HIT ICD-9-CM code and Study Design.

(A) Sensitivity/specificity analysis of HIT ICD-9-CM code. Discharges from a local hospital during the most recent year of the study period were analyzed as described. (B) Study Design. Thrombosis, bleeding, amputations, death, hospital length of stay (LOS) and hospital charges were evaluated in non-HIT discharges and in discharges with a secondary diagnosis of HIT after exclusion of those with history of thrombosis. These outcomes were also evaluated in discharge subgroups with cardiopulmonary bypass, hemodialysis, hip/knee arthroplasty procedure codes, and diagnosis of trauma/injury and gingival/periodontal disease.

Figure 1.. HIT ICD-9-CM code and Study Design.

(A) Sensitivity/specificity analysis of HIT ICD-9-CM code. Discharges from a local hospital during the most recent year of the study period were analyzed as described. (B) Study Design. Thrombosis, bleeding, amputations, death, hospital length of stay (LOS) and hospital charges were evaluated in non-HIT discharges and in discharges with a secondary diagnosis of HIT after exclusion of those with history of thrombosis. These outcomes were also evaluated in discharge subgroups with cardiopulmonary bypass, hemodialysis, hip/knee arthroplasty procedure codes, and diagnosis of trauma/injury and gingival/periodontal disease.

Figure 2.. HIT burden and associations with Age and Sex.

(A) The HIT burden was stable at ~20,000 per year during the study period. The abscissa denotes year of study and ordinate shows the weighted frequency of HIT. Error bars denote 95% CIs. The horizontal dotted line indicates the mean of weighted frequencies over the 5-year study period. (B) High Median age in HIT discharges. Abscissa denotes HIT vs. non-HIT discharges and the ordinate depicts median age of patient and interquartile range (IQR). (C-D) Adjusted odds ratio of HIT was significantly higher in older patients (C) and males overall (D). *** denotes p<0.0001. ns-not significant. CPB- Cardiopulmonary bypass.

Figure 3.. HIT in discharge subsets, and Thrombosis/Bleeding complication rates

(A) Incidence of HIT in discharge subsets. Abscissa denotes patient subgroup by diagnosis/procedure type. Percent of discharges within each subset that had a diagnosis of HIT are shown on the ordinate. Error bars denote standard error (SE). The horizontal dotted line indicates percent of all discharges that had a diagnosis of HIT. (B) Thrombosis in patients assigned a discharge diagnosis of HIT. Abscissa denotes type of thrombosis and ordinate shows the percent of discharges with thrombosis codes. Error bars denote standard error (SE). The solid and dotted horizontal lines indicate thrombosis rates in HIT and non-HIT discharges, respectively. (C) Bleeding in patients assigned a discharge diagnosis of HIT. Abscissa denotes type of bleeding and ordinate shows the percent of discharges with bleeding codes. Error bars denote standard error (SE). The solid and dotted horizontal lines indicate bleeding rates in HIT and non-HIT discharges, respectively.

Figure 4.. In-hospital mortality and association with Thrombosis/Bleeding.

(A) Thrombosis and bleeding were more common in patients who had a fatal outcome. Abscissa denotes fatal and non-fatal outcomes in HIT and non-HIT discharges. The ordinate shows the percent of discharges with thrombosis or bleeding codes. Error bars denote standard error (SE). (B) In-hospital mortality in patients with bleeding or thrombosis. Abscissa denotes thrombosis or bleeding in HIT and non-HIT discharges. The ordinate shows the percent of discharges that reported patient death. Error bars denote standard error (SE). *** denotes p<0.0001.

Figure 5.. Incidence and time to in-hospital mortality, Length of stay and Hospitalization Charges.

(A) Adjusted odds ratio of death is high in HIT discharges. The gingival/ periodontal disease subgroups had too few events to be included in the analysis. (B) Time to in-hospital death in HIT vs. non-HIT discharges. Abscissa denotes HIT or non-HIT discharges. The ordinate depicts median time to death and interquartile range (IQR). (C) Length of stay. The ordinate depicts median length of stay and IQR. (D) Hospitalization charges. The ordinate depicts median hospitalization charges and IQR. ***, ** and * denote p<0.0001, p<0.001 and p<0.01, respectively. ns-not significant