Distinguishing and overlapping laboratory results of thrombotic microangiopathies in HIV infection: Can scoring systems assist?

BACKGROUND: Patients with Human Immunodeficiency Virus (HIV) infection are at risk of thrombotic microangiopathies (TMAs) notably thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). Overlap between laboratory results exists resulting in diagnostic ambiguity. METHODS: Routine laboratory results of 71 patients with HIV-associated TTP (HIV-TTP) and 81 with DIC with concomitant HIV infection (HIV-DIC) admitted between 2015 and 2021 to academic hospitals in Johannesburg, South Africa were retrospectively reviewed. Both the PLASMIC and the International Society of Thrombosis and Haemostasis (ISTH) DIC scores were calculated. RESULTS: Patients with HIV-TTP had significantly (P < .001) increased schistocytes and features of hemolysis including elevated lactate dehydrogenase (LDH)/upper-limit-of-normal ratio (median of 9 (interquartile range [IQR] 5-12) vs 3 (IQR 2-5)) but unexpectedly lower fibrinogen (median 2.8 (IQR 2.2-3.4) vs 4 g/L (IQR 2.5-9.2)) and higher D-dimer (median 4.8 (IQR 2.4-8.1) vs 3.6 g/L (IQR 1.7-6.2)) levels vs the HIV-DIC cohort. Patients with HIV-DIC were more immunocompromised with frequent secondary infections, higher platelet and hemoglobin levels, more deranged coagulation parameters and less hemolysis. Overlap in scoring systems was however observed. CONCLUSION: The laboratory parameter overlap between HIV-DIC and HIV-TTP might reflect a shared pathogenesis including endothelial dysfunction and inflammation and further research is required. Fibrinogen in DIC may be elevated as an acute phase reactant and D-dimers may reflect the extensive hemostatic activation in HIV-TTP. Inclusion of additional parameters in TMA scoring systems such the LDH/upper-limit-of-normal ratio, schistocytes count and wider access to ADAMTS-13 testing may enhance diagnostic accuracy and ensure appropriate utilization of plasma.

Thrombotic thrombocytopenic purpura (TTP)-like syndrome in the HIV era.

BACKGROUND: The thrombotic microangiopathies (TMAs) is a heterogeneous group of relatively uncommon but serious disorders presenting with thrombocytopenia and microangiopathic haemolysis. Thrombotic thrombocytopenic purpura (TTP) is one of these microangiopathic processes. HIV infection is an acquired cause of TTP but the pathogenesis is poorly understood. HIV-associated TTP was previously described to be associated with advanced immunosuppression. The incidence of HIV-related TTP was expected to decline with access to anti-retroviral therapy (ART). METHODS: We undertook an observational study of patients with a diagnosis of TTP admitted to our hospital (CMJAH). The patient demographics, laboratory test results and treatment outcomes were recorded. RESULTS: Twenty-one patients were admitted with a diagnosis of TTP during the study period. All patients had schistocytes and severe thrombocytopaenia. The presenting symptoms were non-specific and renal dysfunction and neurological compromise were uncommon. 77% of the patients were HIV-infected and, in 7 patients, TTP was the index presentation. The remainder of the HIV infected patients were on ART and the majority were virologically suppressed. A significant female preponderance was present. Only 4 of the 21 patients tested HIV negative with a positive Coombs test in 2. All patients in this cohort received treatment with plasma exchange therapy for a median period of 12 days with a 96.5% survival rate. Neither the baseline laboratory features nor the degree of immunosuppression was predictive of the duration of therapy needed for remission. CONCLUSION: HIV-related TTP is still a cause of morbidity and the clinical presentation is heterogeneous which may present a diagnostic challenge in the absence of sensitive biomarkers. Early treatment with plasma exchange is effective but expensive and invasive.

Combination of acquired von Willebrand syndrome (AVWS) and Glanzmann thrombasthenia in monoclonal gammopathy of uncertain significance (MGUS), a case report.

BACKGROUND: Autoimmune paraphenomena, are associated with B-cell lymphoproliferative disorders, including monoclonal gammopathy of uncertain significance. These paraphenomena can rarely include acquired bleeding disorders. CASE PRESENTATION: This case study reports an unusual clinical presentation of 2 acquired bleeding disorders, Acquired von Willebrand syndrome (disease) and Acquired Glanzmann's thrombasthenia, in an elderly patient with monoclonal gammopathy of uncertain significance. CONCLUSIONS: Acquired bleeding disorders are often underdiagnosed and a high degree of clinical suspicion is required. The patient in this study demonstrated platelet aggregometry which was atypical for isolated Glanzmann's thrombosthenia because of the severe concomitant endogenous decrease in von Willebrand factor. There was an absence of platelet aggregation to all tested agonists including ristocetin. Once the diagnosis was made, however, the patient showed a partial response to intravenous immunoglobulin confirming the immunological pathogenesis in this case. This case highlights the need to consider acquired bleeding disorders in patients with a possible predisposing factor.