Microangiopathic Hemolytic Anemia as the First Manifestation of Lung Adenocarcinoma

Anemia is common in patients with disseminated carcinoma and is usually due to bleeding, infection, or marrow suppression from chemotherapy or metastatic infiltration. However, microangiopathic hemolytic anemia is rarely seen in such patients. We report a case in which microangiopathic hemolytic anemia was the initial finding in lung adenocarcinoma.

Snakebites and microvesicles: Popping bubbles

Commentary by Lawrence D. Longo, MD

Background and Aims Thrombotic microangiopathy (TMA) is a diagnosis made on tissue biopsy manifesting as acute organ dysfunction. It has a variety of causes broadly categorised as: primary hereditary/genetic, primary acquired, secondary, and infection-related [1]. On blood testing there is evidence of microangiopathic haemolytic anaemia (MAHA) –, thrombocytopenia, raised lactate dehydrogenase (LDH), reduced haptoglobin and fragments on blood film. Renal involvement with acute injury is evidenced by an elevation in creatinine; together with MAHA this is haemolytic uraemic syndrome (HUS). We sought to examine the TMA/MAHA population as it presented to nephrology in the West of Scotland and evaluate if there was differences in presentation between TMA with and without MAHA. Method This is a retrospective case series of adult nephrology patients. We extracted health data from the west of Scotland renal electronic patient records database Strathclyde Electronic Renal Patient Record (“SERPR”) provided by VitalDataClient. We ran a query to identify patients in whom TMA and/or MAHA and/or HUS was inputted as a diagnosis. 363 patients were identified. Each was manually inspected. Patients were excluded who were not suitable for inclusion (e.g. paediatric data, incomplete records, patients without relevant diagnoses). Non-parametric Kruskal Wallis testing was used via R statistical software. Results 134 patients were identified. The underlying diagnoses were: hypertension (n = 34), the atypical HUS (aHUS, n = 22), drug-induced (n = 17), autoimmune (n = 12,), thrombotic thrombocytopenic purpura (n = 12), malignancy (n = 10), inflammatory (n = 10), peri-partum (n = 9). Others included: transplant-related, unknown, Ecoli 0157, diarrhoea-related, IgA, AAV, MPGN, and essential thrombocythaemia. Note: many patients had multiple possible contributors to their diagnosis. The average biochemical levels at presentation were: creatinine 591umol/L; haemoglobin 82; platelet count 98.7; LDH 1674.2; bilirubin 34.5. Renal recovery was observed in n = 27 (19%); CKD3 n = 32 (24%); CKD4 n = 10(7%); CKD5 n = 7(5%); those who have progressed to ESRF (requiring renal replacement therapy) n = 40(31%); persisting transplant function n = 5(4%). 15 patients died (10%). We categorised patients into 3 groups. 1 – presence of TMA on biopsy without MAHA (n = 28). 2 – TMA on biopsy plus evidence of MAHA (n = 41). And 3 – MAHA in those not biopsied (n = 62). 3 patients with MAHA did not have TMA on biopsy. Those in group 1 had on average a lower serum creatinine at 331umol/L compared with group 2 (634 umol/L) and group 3 (666 umol/L). This result was significant p <0.05. Hypertension was a leading cause in groups 1 and 2. aHUS was not present in group 1 - all patients presented with MAHA. All peri-partum patients were in group 3 i.e. not biopsied. Conclusion It is evident from the dataset that hypertension is a major contributor to acute and chronic renal impairment. With aHUS contributing to a significant number of cases, given the advances in testing and therapeutics, early liaison with national services in complement disorders is paramount to protecting the kidneys. With 19% of patients regaining an eGFR >60ml/min prompt investigation is crucial to reducing the burden of disease. Long term renal follow-up should be offered. 21% of patients had no evidence of MAHA –we should be wary of excluding a TMA process in the absence of MAHA.

<h3>To the Editor.—</h3> Microangiopathic hemolytic anemia (MAHA) may be found to be associated with several entities, including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura, and cancer.¹We describe a patient who, together with having familial antecedents of HUS, presented with MAHA and adenocarcinoma of the lung. Pathology findings suggested the carcinoma to be related to the pathogenicity of the microangiopathic anemia. To our knowledge, this is the first description of the unusual association of familial HUS with MAHA and carcinoma. <h3>Report of a Case.—</h3> A 35-year-old man had familial antecedents of HUS. His son, sister, and niece had relapsing familial HUS, and all three, as well as our patient and a brother, had HLA haplotype A3,B7 with persistent hypocomplementemia through alternative pathway activation. Forty days before admission to hospital the patient became ill with sustained fever and discomfort in the lower right side of the jaw and lost 12

449. Management of microangiopathic haemolytic anaemia in pregnancy

The prevalence and clinical outcomes of microangiopathic hemolytic anemia in patients with biopsy-proven renal thrombotic microangiopathy.

In the past, thrombotic thrombocytopenic purpura (TTP) was defined as a syndrome of the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurologic deficits, renal abnormalities and fever. To include patients with incomplete features, the pentad definition was replaced by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and neurologic deficits; or the diad of thrombocytopenia and MAHA. None of these definitions provides a clear distinction of TTP from atypical hemolytic uremic syndrome (aHUS) or other causes of the syndrome of MAHA and thrombocytopenia or thrombotic microanangiopathy. This brief review describes a mechanistic definition of TTP, provides a framework for assessing the role of various co-morbid conditions in the pathogenesis of the syndrome of thrombocytopenia and MAHA, and summarizes new insights of the natural course of TTP. Based on these new insights, a strategy of ADAMTS13-guided preemptive rituximab therapy is proposed to prevent relapses in patients with acquired TTP. Thrombotic thrombocytopenic purpura (TTP) has been defined as a clinical syndrome of pentad (thrombocytopenia, microangiopathic hemolytic anemia [MAHA], neurological deficits, fever and renal abnormalities), triad (thrombocytopenia, MAHA, neurological deficits) or diad (thrombocytopenia and MAHA). In addition to this uncertainty, there was also no consensus on whether and how patients with prominent renal failure or co-morbid conditions should be excluded. The difficulty of defining TTP as a clinical syndrome arises from two facts: More than one disorder may cause the syndrome of diad, triad or pentad; and some patients of TTP do not present with thrombocytopenia or MAHA.

Cancer du sein et microangiopathies thrombotiques paranéoplasiques

A case of microangiopathic hemolytic anemia (MHA) associated with disseminated breast cancer is reported. A 57-year-old woman was admitted for evaluation of a tumor of the left breast. She had had lumbago for about 6 months prior to the admission. A few days after the admission, she received red blood cell transfusion and she developed a bout of hemolysis immediately after that. The hematological examinations showed hemolytic anemia in association with severe red blood cell fragmentation and leukoerythroblastosis. While clotting abnormalities or thrombocytopenia was quite mild at the height of the hemolytic crisis. On the other hand, the histology of the left breast tumor revealed papillotubular adenocarcinoma and the Ga-citrate scintigram showed diffuse RI uptake at the spine especially in the lumbar region. Taken altogether, she was diagnosed as having disseminated breast cancer and MHA without disseminated intravascular coagulation (DIC). Then she was started on combination chemotherapy using CMFVP regimen, and anti-estrogen therapy. About 4 months later, MHA was brought to remission with the remarkable reduction of the tumor bulk at both the primary and metastatic sites, and she was discharged. A month after that, however, she entered the hospital again because of the rapid progression of anemia attributable to relapsing MHA. On the 17th hospital day of this admission she died of respiratory failure.The autopsy disclosed diffusely infiltrative, though partly nodular, metastatic tumor growth of thoracic and lumbar vertebrae. In addition, there were a number of tumor emboli in the small vessels of both lungs and severe cryptococcal infection in both pulmonary bases as well. But there were no thrombi formation in any organs to suggest the presence of DIC.To conclude, the case depicted here is quite intriguing in view of the pathogenesis of MHA unassociated with DIC, unfavorable effect of blood transfusion for MHA and the possible efficacy of chemotherapy against malignancy-related MHA.

Atypical presentation of relapsed multiple myeloma with microangiopathic hemolytic anemia

It has been a great ride: The history of HELLP syndrome

Background:Microangiopathic hemolytic anemias (MAHA) are characterized by the presence of hemolytic anemia (HA), related to red blood cell (RBC's) fragmentation, thrombocytopenia and hemosiderinuria due the intravascular hemolysis. The term thrombotic microangiopathy (TMA) is also used to describe syndromes characterized by AHMA, thrombocytopenia, and thrombotic lesions in small blood vessels such as Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic uremic syndrome (HUS). Although TTP and HUS are the prototypes of TMA / MAHA, there are other causes that should not be forgotten, such as MAHA by valvular leak.Aims:Perform the casuistry of the Hematology Service of a Central Hospital for a rare cause of hemolytic anemia.Methods:Parameterized search for the data of patients with MAHA and hemosiderinuria evaluated at a Hematology out patients clinic at a Central Hospital between January 2007 and March 2018.Results:9 patients with MAHA were identified with valvular leak, the mean age at diagnosis was 68 years and 6 were men (66%). All patients had mechanical heart valves: 66% mitral valve, 22% aortic valve and 11% both valves. The time from surgery to diagnosis of AHMA was ∼ 2 years. The mean Hb value was 8.4 mg/dL. All patients had RBC fragmentation. The mean value of DLH was 3773U/L, total bilirubin (TBil) was 1.9 mg/dL. 88% patients were supplemented with oral iron. Only 3 patients increase ∼ 1.5 g of Hb after 3 months of therapy. 1/3 patients were supplemented with EV iron; 1/3 needed blood transfusion. 66% underwent valvular leakage correction and of these 50% significantly improved Hb and hemolysis.Summary/Conclusion:A careful clinical history and the RBC morphology play a central role in the diagnosis of anemia. The MAHA due to leak valvular is a rare entity, but with a tendency to increase. Despite the small number of patients, the authors consider pertinent to present these data because this is a potentially reversible cause of anemia. The disproportionate high DHL level in relation to the TBilis a possible clue to the differential diagnosis of HA.

A syndrome, including microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal insufficiency, has been recognized to occur as a complication of antineoplastic therapy with mitomycin. The clinical presentation can vary from a chronic course with mild anemia and slowly progressive renal dysfunction to a fulminant course with severe anemia, rapid deterioration of renal function, and death. The optimal treatment of the mitomycin-associated MAHA syndrome is unknown. Therapy with steroids, antiplatelet agents, and heparin sodium has failed to reverse the MAHA. Plasmapheresis has improved the MAHA in a few patients without reversing the renal failure. We treated two patients who had MAHA and renal dysfunction during chemotherapy that included mitomycin; the MAHA and hypertension both objectively improved after treatment that included vincristine sulfate.

Microangiopathic hemolytic anemia (MAHA), is one of the causes of extra vascular hemolysis. It is seen in settings with pathologically altered small blood vessels. Disseminated carcinomas may rarely present as MAHA. A case of a 28 year old female with carcinoma stomach, who presented with MAHA as a first manifestation is reported. Acute onset of MAHA, may be the first manifestation of malignancy. In the absence of relatively common causes like disseminated intravascular coagulation,/Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, MAHA warrants extensive rapid investigations including bone marrow aspiration for possible metastatic deposits.