Cancer-Related Microangiopathic Hemolytic Anemia Clinical and Laboratory Features in 168 Reported Cases (original) (raw)
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Cancer-related microangiopathic hemolytic anemia
Transfusion, 2016
Cancer-related microangiopathic hemolytic anemia (CR-MAHA) is a paraneoplastic syndrome characterized by Coombs-negative hemolytic anemia with schistocytes and thrombocytopenia. We reviewed and analyzed all cases of CR-MAHA reported since 1979 (the time of the last published review on this topic) according to predefined criteria. We found 154 cases associated with solid cancer and 14 with lymphoma. Among the solid cancers, gastric, breast, prostate, lung, and cancer of unknown primary (CUP) were most common; 91.8% of cancers were metastatic, and in 19.4% of solid cancers CR-MAHA did not occur until recurrence of cancer. Lymphoma cases included Hodgkin disease, angiotropic lymphoma, diffuse large cell lymphoma, and myeloma. Evaluation of the clinical and laboratory findings revealed that only a minority of cases presented with the features of thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic uremic syndrome (aHUS), with the exception of prostate cancer, where aHUS was a common presentation. Compared to hereditary or immune TTP or aHUS, disseminated intravascular coagulation and pulmonary symptoms were more common in CR-MAHA. Plasma exchange or fresh frozen plasma was rarely effective except in prostate cancer patients with aHUS. CR-MAHA responded to antitumor therapy in many patients with gastric, breast, lung, and CUP cancers. These patients had a superior survival compared to patients without chemotherapy. Compared to the prognosis of patients with metastatic cancer without CR-MAHA, the prognosis of CR-MAHA patients was greatly inferior. There is evidence that some cases of CR-MAHA in lymphoma are immune mediated. (Medicine 2012;91: 195Y205) Abbreviations: ADAMTS = a disintegrin-like and metalloprotease with thrombospondin type 1 repeats, aHUS = atypical hemolytic uremic syndrome, CR-MAHA = cancer-related microangiopathic hemolytic anemia, CUP = cancer of unknown primary, DIC = disseminated intravascular coagulation, MAHA = microangiopathic hemolytic anemia, NHL = non-Hodgkin lymphoma, TTP = thrombotic thrombocytopenic purpura.
Cancer, 1981
Microangiopathic hemolytic anemia and thrombocytopenia secondary to disseminated intravascular coagulation is a well-described complication of widely metastatic carcinoma. The authors report four cases of gastric carcinoma, one case of colon cancer, and one case of adenocarcinoma of unknown primary in which the patient developed a syndrome analagous to thrombotic thrombocytopenic purpura, consisting of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure without definite evidence of disseminated intravascular coagulation. In contrast to previous reports, postmortem examination in three of the cases revealed no recurrence or only microscopic foci of residual tumor. In the remaining three, there was clinical and pathologic evidence of grossly disseminated carcinoma. Also in contrast to previous cases, all patients evidenced azotemia and proteinuria at the onset of the syndrome and ultimately uremia was a contributing cause of death. Coagulation profiles showed prolonged thrombin times and elevated fibrin degradation products in four instances and did not distinguish the patients with grossly metastatic disease from those with no tumor or only microscopic residua. Circulating immune complexes containing carcinoembryonic antigen were found in the patient with metastatic colon carcinoma. The syndrohe was clinically identical whether or not grossly metastatic tumor was present, and it should not be attributed to advanced disease without definite clinical or pathologic evidence of a recurrence.
PubMed, 1994
From January of 1990 to June of 1993 a diagnosis of microangiopathic hemolytic anemia (MHA) was made in 5 out off 121 new patients with malignant tumor. There were 3 females and 2 males, with a mean age of 57 yr (range: 43-75), and a primary tumor in stomach (n = 2), pancreas (n = 1) and of unknown origin (n = 2). In all cases histologic type was adenocarcinoma and diagnosis was obtained by marrow examination. Four patients developed a disseminated intravascular coagulation syndrome. Intravascular deposits of fibrin, intimal proliferation and tumoral microembolisms were noted in 2 cases. Patients did not received chemotherapy, and the median survival was 7 days (range: 3-61).
Journal of Medicine, 2019
Microangiopathic Hemolytic Anemia (MAHA) is a hematological condition which is very rare for the primary presentation of a gastric adenocarcinoma with bone marrow metastases. When it emerges as initial findings in a previously undetected case of malignancy, the diagnosis is often missed and results in inappropriate management. Carcinoma stomach associated with MAHA is generally having fulminant course. This is a case report of a 30-year-old male who presented with widespread bone marrow infiltration along with Coomb's negative haemolytic anemia, thrombocytopenia and schistocytes in peripheral blood typical of MAHA. The combination of MAHA and bone marrow infiltration in gastric adenocarcinoma is a very rare entity. When the cause of progressive MAHA is unknown, the possibility of cancer-associated MAHA must be excluded by performing additional tumor workup, including the detection of tumor markers, Endoscopy of upper GIT, colonoscopy, bone marrow examinations, and PET-CT or bone scans.
British Journal of Haematology, 2001
Complete deficiency of von Willebrand factorcleaving protease (VWF-cp) has recently been identified as a pathogenetically important factor for thrombotic thrombocytopenic purpura (TTP). Microangiopathic haemolytic anaemia (MAHA) with thrombocytopenia in patients with metastasizing neoplasms is clinically similar to TTP, however, the pathogenesis of the condition is unclear. Partial deficiency of VWF-cp in metastasizing malignancy has recently been reported in patients without MAHA. Our study shows normal or subnormal VWF-cp activity in four patients with metastasizing neoplasia-associated MAHA but, in contrast to classical TTP, no complete deficiency of VWF-cp despite the full clinical picture of MAHA.
Breast Cancer Research
Background Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA. Methods Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records. Results Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2−, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had...
Community Oncology, 2005
The occurrence of microangiopathic hemolytic anemia and thrombocytopenia in patients with disseminated malignant disorders has been well documented. However, when systemic malignancy is not clinically apparent, these features may be misdiagnosed as thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS), and patients may be treated with plasma exchange, a procedure with substantial risk. Among the 329 patients in the Oklahoma TTP-HUS Registry, 1989-2005, 12 patients who were treated with plasma exchange for presumed TTP-HUS were later found to have a systemic malignancy. Details about one such patient, a 52-year-old woman who had a history of breast cancer, are presented. Although some of her clinical features were atypical for TTP-HUS, and the possibility of recurrent breast cancer was carefully considered, no evidence of cancer was found and plasma exchange treatment for TTP-HUS was initiated. Disseminated breast cancer was not revealed until a microscopic examination of tissue sections was made at autopsy. In retrospect, a bone marrow biopsy might have documented the presence of metastatic cancer in this patient. Hematologists/ oncologists must be aware that patients with clinically diagnosed TTP-HUS may have an occult systemic malignant disorder.
Thrombotic microangiopathy in cancer
Thrombosis Research
Thrombotic microangiopathy (TMA) is a rare but often devastating complication of cancer and cancer treatment. The syndrome is defined by thrombocytopenia (i.e., a platelet count of < 150,000/mL blood, or a reduction in platelet count by > 30% from baseline), evidence of microangiopathic hemolytic anemia (MAHA), and evidence of organ damage. There are nine recognized categories TMA including thrombotic thrombocytopenic purpura (TTP) hereditary and acquired deficiency of the von Willebrand cleaving protease, ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), congenital and acquired atypical hemolytic uremic syndrome (aHUS), Shiga toxin-related hemolytic uremic syndrome (STEC-HUS), metabolic causes due to abnormalities both congenital and acquired defects in the cobalamin pathway, coagulation disorders such as disseminated intravascular coagulation (DIC), drug-induced TMA due to direct toxic effects as well as immune-mediated endothelial damage, cancer, and chemotherapeutic treatment. 1,2 TMA has also been seen in clinical settings of inflammatory autoimmune disorders, including systemic lupus erythematosus and rheumatoid arthritis, the glomerulopathies, and bone marrow or solid organ transplantation. The presentations of TMA disorders may be indistinguishable clinically. Although the pathophysiology of the disorders varies, all are characterized by endothelial damage resulting in microvascular ischemia. 1,2 This review will discuss, in detail, TMA uniquely associated with cancer and cancer treatment. A simplified summary of causes, pathology, and treatment of cancer-associated TMAs can be found in ►Table 1. Tumor-Associated Thrombotic Microangiopathy Almost 50 years ago, TMA was first described in gastric cancer patients. Cancer is known to be associated with both macroand microvascular thrombosis. 1 TMA was reported with mucinous gastric cancers from as early as the 1970s. 3-5 Cobalamine deficiency, which can also cause a TMA-like syndrome by itself, can occur in gastric cancer and may contribute to the development of TMA in that setting. 6 In most cases, TMA is associated with advanced cancer. It has been identified in patients with metastatic gastric, ovarian cancer, prostate, lung cancer, urothelial cancers, lymphomas, and myeloproliferative neoplasm and acute myeloid leukemia. 7-10 Tumor embolization to the small vessels in the lungs, particularly from gastric, urothelial, and lung cancers, is associated with pulmonary tumor thrombotic microangiopathy (PTTM). 7-12 In one study, it occurred in 21/690 consecutive autopsies and is reported to occur in 0.3 to 3.3% of autopsies. This syndrome is associated with acute pulmonary decompensation, characterized by worsening dyspnea, and pulmonary hypertension. In addition to hypoxemia, the chest X-ray findings show ground glass opacities, without an infectious etiology. Pathologic findings include small vessel, pulmonary arteriolar occlusion with intimal proliferation, and fibrin deposition in the thrombi. 9,10 There is evidence of increased pulmonary vascular resistance. 7,11 The syndrome is rapidly fatal. 9,10 Pathologic features of tumor-induced TMA include vessel wall thickening at the arteriolar-capillary junction, with
Microangiopathic Haemolytic Anaemia and Mucin-forming Adenocarcinoma
British Journal of Haematology, 1970
Dyspepsia Weight loss. anaemia, abdominal pain, hepato-splenomegaly Dyspepsia Anaemia, splenomegaly Back pain Anaemia, bone metastases Chest pain Anaemia, bilateral leg vein thrombosis Abdominal pain, haematuria and spontaneous Anaemia, abnormal barium meal
Hemophagocytic Lymphohistiocytosis in Chronic Lymphocytic Leukemia
Journal of Clinical Oncology, 2011
A 59-year-old woman with known stage 3 chronic lymphocytic leukemia (CLL) presented with increasing lymphocytosis and progressive cytopenias. Full blood count revealed hemoglobin 8.9 g/dL, WBC count 13.3 ϫ 10 9 /L, neutrophil count 1.8 ϫ 10 9 /L, lymphocyte count 11.0 ϫ 10 9 /L, and platelets 101 ϫ 10 12 /L. Bone marrow examination (Fig 1A, hematoxylin and eosin [HE] stain) was consistent with disease progression, showing markedly hypercellular bone marrow resulting from interstitial infiltrate of CLL cells coexpressing CD20, CD79a, CD19, CD5, and CD23. Previous treatments included single-agent chlorambucil 7 years before and single-agent fludarabine 5 years before. Therefore, she was administered fludarabine and cyclophosphamide chemotherapy and received her first cycle without complications. After the initial cycle of chemotherapy, the patient was admitted with febrile neutropenia. Broad-spectrum antibiotics were administered. An infection screen, including blood, urine, and sputum cultures and a viral nasal swab, was negative. The patient remained pancytopenic 25 days after chemotherapy, so subcutaneous granulocyte colony-stimulating factor was commenced. On the presumption that the cytopenia represented either ongoing disease or delayed marrow recovery after chemotherapy, a trephine biopsy was performed, which demonstrated markedly hypercellular bone marrow (Fig 1B, HE stain) resulting from a prominent population of CD68ϩ macrophages arranged in sheets (Fig 2A, CD68 stain). There was evidence of phagocytic activity in some areas, consistent with a hemophagocytic syndrome. A minor component of residual CLL infiltration also remained. In light of these findings, additional investigations were performed. Serum ferritin was 12,000 g/L