Numerous Schistocytes Research Articles

Thrombotic Thrombocytopenic Purpura (ADAMTS13 [a Disintegrin and Metalloproteinase With a Thrombospondin Type 1 Motif, Member 13] Deficiency) as Cause of Recurrent Multiterritory Ischemic Strokes.

Thrombotic Thrombocytopenic Purpura (ADAMTS13 [a Disintegrin and Metalloproteinase With a Thrombospondin Type 1 Motif, Member 13] Deficiency) as Cause of Recurrent Multiterritory Ischemic Strokes.

Bortezomib As Frontline Therapy in the Management of TTP

IntroductionThe current International Society on Thrombosis and Hemostasis (ISTH) guideline of Thrombotic Thrombocytopenic Purpura (TTP) recommends Therapeutic Plasma exchange (TPE) and corticosteroid in the management of TTP, with Rituximab and Caplasizumab as additional potential therapies [X Long Zheng et al, J Thromb Haemost. 2020;18:2496-2502]. This potentially fatal condition requires prompt diagnosis and treatment but large volume plasma treatment is not without risk and in settings with limited access with sufficient compatible plasma for apheretic exchange, this can delay this emergency therapy. We have been running the first therapeutic apheresis services with an Optia instrument in Uganda at the Joint Clinical Research Centre in Kampala city and TTP is the main indication for TPE. We present 2 recent sequential cases of TTP that were successfully managed when Bortezomib was combined with plasma therapy.Case1.A 25yr woman referred to our service on 29/09/2020, with recent onset of bruising, icterus, severe anemia Hgb5.7g/dL, Severe thrombocytopenia 8 x 10 3/uL, a high LDH 3909U with schistocytes on the peripheral blood film severe thrombocytopenia and a negative Direct Antiglobulin test. She was Blood Group B+. She was managed with 3 sessions of TPE of 2.1, 1.1 and 2.0 plasma volume exchanges with 6727mL, 3026mL and 5459mL of replacement plasma respectively and oral prednisone 60mg daily without remission. Subsequent quantities of plasma were insufficient for apheresis and were instead transfused. She also received weekly Rituximab 500mg (IV) but without significant recovery in the platelet count until she received Bortezomib 2mg (SC) when there was corresponding recovery of the platelet count and with each dose to a total of 4 doses (Figure 1).Case2.A 55yr man was previously well and shopping in a mall when he had an index episode of seizures on 19.Jun.2021 and was hospitalized that day with altered consciousness and focal motor signs. He required intubation for 3 days and at the time of hospitalization, he had Hgb 9gm/dL, PLT 17 x 10 3/uL, LDH2177U, with numerous schistocytes on the peripheral blood film and a negative Direct Antiglobulin Test. The baseline blood sample functional ADAMTS13 was 3% and had Blood Group AB+. He had received the 1 st dose of the Astra-Zeneca Covid19 vaccine on 06.May.2021. It was not possible to get any AB plasma and we considered it risky to perform large volume TPE with non-AB plasma and he was instead treated with daily transfusion with Group A+ Plasma concurrent with daily Prednisone 60mg. Because of our previous experience of poor response to Rituximab, we opted to treat him upfront with 4 doses of 2mg bortezomib (SC) given 3 days apart. He made brisk recovery to complete remission and was discharged for weekly outpatient CBC and LDH monitoring. His platelet count subsequently dropped without a corresponding drop in the Hgb and no rise in the Hgb. We initially re-hospitalized him for 4 more days of plasma transfusion but without a brisk response and since the LDH was not increasing, the isolated Thrombocytopenia was considered a side effect of Bortezomib that was expected to resolve and he receive no further treatment but continued to recover to complete remission as an out-patient (figure 2).Discussion:Our findings suggest a possible role for Bortezomib in frontline therapy for TTP with potential to reduce the plasma requirement in TPE and this approach warrants a randomized clinical trial. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Bortezomib Indicated in the management of Multiple Myeloma and Plasma Cell Dyscrasia

A Challenging Case of Atypical Hemolytic Uremic Syndrome in a Young African American Patient

BackgroundIt is known that malignant hypertension (mHTN) and thrombotic microangiopathy (TMA) commonly coexist. Deciding which phenomenon preceded the other remains a clinical dilemma, specifically in African American patients. However, making that determination is of utmost importance because the management will be different, and that can have dramatic effects on prognosis and outcomes. Herein, we report a case of atypical hemolytic uremic syndrome (aHUS) presenting as mHTN.Case PresentationA 35-year-old African American male with known history of hypertension, presented with nausea, vomiting, and diarrhea for four days. He also reported fatigue and exertional shortness of breath. Upon presentation, his blood pressure was 260/160 mmHg, otherwise physical exam was unremarkable. Initial work up showed hemoglobin of 8.8 g/dL (baseline 13.5), platelet count of 21,000/mL (baseline 250,000), serum creatinine of 16.99 mg/dL (baseline 0.99), MCV (84 fl), increased reticulocyte production index (3.58), increased LDH (1709 U/L), undetectable haptoglobin, and numerous schistocytes on peripheral blood smear. He was admitted as a case of hypertensive emergency and TMA. IV labetalol and hemodialysis were started. Given his gastrointestinal symptoms; stool for Shigella and E.Coli O157:H7 were checked and they were negative.Given the severity of his hematologic derangements and difficult to control blood pressure, we decided to proceed with renal biopsy to rule out primary aHUS which showed thrombotic microangiopathy, global glomerulosclerosis, moderate interstitial fibrosis and tubular atrophy suggestive of aHUS or rheumatologic disorders like systemic sclerosis and arguing against malignant HTN as the sole player. ANA and anti-Scl-70 antibodies were negative. Final impression was aHUS by exclusion, and patient received meningococcal vaccines (Menactra and Bexsero) in preparation to start eculizumab. aHUS genetic panel was sent which came back equivocal as it showed mutations of unknown significance (homozygous missense mutation in the MASP2 gene and 2 heterozygous mutations in the C2 gene).He was started on eculizumab 900 mg weekly for 4 weeks then 1200 mg biweekly starting week 5. He was seen in the office 2 months after initial presentation and receiving 5 doses of Eculizumab. His kidney function showed improvement with > 2 liters of urine output daily, blood pressure was better controlled. A decision by nephrology was made to give him a break from dialysis and remains dialysis-free a year later.DiscussionaHUS is a rare disorder with an estimated prevalence of seven per one million children in Europe. It causes uninhibited activation of complement factors that leads to renal endothelial damage and activation of coagulation cascade leading to TMA. The diagnosis of aHUS requires the fulfillment of the classical triad (microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure) with a positive gene mutation or antibodies to complement factors. However, absence of these mutations or antibodies, as in the presented case, do not exclude the diagnosis. The early diagnosis of aHUS is necessary for treatment with eculizumab, a monoclonal antibody against C5 to block the terminal complement cascade. Kidney biopsy can be helpful in equivocal cases especially if it shows only the typical changes of malignant hypertension which essentially rules out aHUS. Hypertension with concurrent TMA is treated with strict BP control which is often enough to resolve TMA features and restores renal function, at least partially. On the contrary, aHUS causing severe HTN needs more sophisticated testing and blockade of the terminal complement component to improve outcome; that's why the distinction of which one is the primary process is of utmost importance. Our case emphasizes the importance of having low threshold for testing for aHUS in patients with mHTN and TMA, especially in African American patients where malignant HTN is known to happen more commonly, and to notice the subtle hints that may help in this distinction, such as profound hemolysis or thrombocytopenia out of proportion to what one would expect from mHTN alone. Early recognition of aHUS may save a patient's kidney. DisclosuresNo relevant conflicts of interest to declare.

Numerous schistocytes in thrombotic thrombocytopenic purpura

An 83-year-old man was transported by ambulance to the emergency room because he had a clouding of consciousness. On arrival, his Glasgow Coma Scale score was 13 (E4V4M5). His temperature...

Congenital Thrombotic Thrombocytopenic Purpura: An Unusual Case of Microangiopathic Haemolytic Anaemia in a Newborn

We present an extremely rare case of hyperbilirubinemia with rapid progression leading to bilirubin encephalopathy in term neonate. Despite early recognition and intervention, death occurred as a total serum bilirubin reached 25 mg/dl. It was a case of Coomb’s negative microangiopathic haemolytic anaemia in a newborn period which is autosomal recessive inheritance i.e. Upshaw-Schulman Syndrome. (Congenital thrombotic thrombocytopenic purpura) characterised by numerous schistocytes on peripheral blood smear, thrombocytopenia , increased reticulocyte count, increased bilirubin and LDH level. This rare disease is often misdiagnosed especially in newborn baby. So we present this case not only for its variety but also for to create more awareness among pathologist and paediatrician as treatment protocol entirely differ.

Microangiopathic Haemolytic Anemia Associated with Bone Marrow Metastasis in a 12 Year Old Child

A 12 year old female child presented to the emergency department of our institute with complaints of generalized weakness and lethargy for three months and rapidly progressive breathlessness of 15 days duration. There was history of episodes of hematemesis and melena. Examination was notable for presence of tachypnea, tachycardia, severe pallor, mild pedal edema, right sided pleural effusion, mild hepatomegaly and splenomegaly. Investigations revealed elevated serum lactate dehydrogenase levels, 2127 IU/L, unconjugated hyperbilirubinemia, 3.3 mg/dl, haemoglobin 8.3 g/dl, total leucocyte count, 18×109/L, platelet count, 30×109/L, and a reticulocyte count of 23.3%. Peripheral blood smear showed numerous schistocytes, polychromasia, circulating nucleated red blood cells

Ciprofloxacin-Induced Thrombotic Thrombocytopenic Purpura: A Case of Successful Treatment and Review of the Literature.

A 49-year-old African American woman was admitted to our hospital with abdominal pain, nausea, vomiting, lethargy, and confusion. She was receiving ciprofloxacin for a urinary-tract infection prior to admission. Laboratory examination revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and serum creatinine. Peripheral smear showed numerous schistocytes, and the patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). Ciprofloxacin was identified as the offending agent. The patient received treatment with steroids and plasmapheresis, which led to rapid clinical recovery. This is the first case to our knowledge of successfully treated ciprofloxacin-induced TTP; previously reported cases had fulminant outcomes. Quinolones are an important part of the antibiotic armamentarium, and this case can raise awareness of the association between quinolones and TTP. A high index of suspicion for detection and early and aggressive management are vitally important for a successful outcome.

Emergency Plasmapheresis in a case of ThromboticThrombocytopenic Purpura (TTP)

An 84 year-old female was admitted to our Department of Vascular Internal Medicine after a sudden onset of weakness on her right side and aphasia along with signs of myocardial ischemia from Electrocardiogram (EKG). Clinical and blood exams led to a suspicion of Moschcowitz syndrome, which was reinforced by the presence of numerous schistocytes on a peripheral blood smear.Due to a rapid deterioration of vital signs as well as alertness, the patient underwent an emergency transfusion and plasmapheresis treatment as recommended by American Society of Apheresis (ASFA) guidelines: one plasma volume was replaced with fresh frozen plasma (FFP) every 24 hours, for the first eight days, in order to reach at least a level of 150,000 platelets/mm3 over three consecutive days accompanied by a decrease in LDH until to 670 UI/l.After this therapy, the clinical picture significantly improved with a complete recovery of consciousness and the disappearance of neurological defects.Examinations to determine the etiology made us hypothesize a secondary status of thrombotic thrombocytopenic purpura due to an autoimmune disorder compatible with Sjogren’s syndrome. The patient was discharged and prescribed prednisone.Currently the patient is in good clinical condition and continues the therapy with prednisone (5 mg/die).

Thrombotic microangiopathy — Do we care why?

Thrombotic microangiopathy (TM) defines a pathology characterised by microangiopathic haemolytic anaemia and thrombocytopenia, which may assume different expressions in several organs. Among the possible causes are malignancy and chemotherapeutic agents (CA) like gemcitabine. We present the case of a 65 year-old male patient, a former smoker, with a known epidermoid lung carcinoma diagnosed in December 2011. He was submitted to treatment with carboplatin plus gemcitabine until March 2012, and tumor regression was achieved. A lobectomy and excision of the involved lymph nodes were performed in April 2012. In November 2012 he presented with anaemia (haemoglobin 6.1 g/dL), severe thrombocytopenia, hyperbilirubinemia and elevated lactate dehydrogenase (>1000 U/L). Numerous schistocytes were present on peripheral smear. Coombs test was negative. There was no evidence of renal failure or neurologic abnormalities. We assumed the diagnosis of TM, and started plasma exchange and high-dose corticosteroids. The performed exams showed a new small liver nodule and a lytic lesion in the iliac bone suggestive of tumor relapse. There was no response to the therapeutic, so plasma exchange was intensified to twice daily. Anyway the patient died of haemorragic complications. Malignancy and CA are rare causes of TM. In both cases, it's a highly fatal disease, and the treatment with plasma exchange is controversial in these patients. This case illustrates how challenging it can be to distinguish, in the clinical practice, a TM associated to malignancy from that caused by antitumor agents used to control those same diseases.

Catastrophic Antiphospholipid Syndrome with Severe Acute Thrombotic Microangiopathy and Hemorrhagic Complications

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening form of the antiphospholipid syndrome characterized by disseminated vascular thrombosis resulting in multiorgan failure. On an exceedingly rare occasion, CAPS can be associated with severe hemorrhagic manifestations. We report a young woman with a history of several spontaneous miscarriages who presented with menorrhagia and hemoptysis. The patient developed respiratory failure due to diffuse alveolar hemorrhage. Laboratory tests demonstrated severe hemolytic anemia, profound thrombocytopenia, markedly elevated fibrin degradation products, and renal failure. Blood films revealed numerous schistocytes. Serologic tests disclosed hypocomplementemia and autoantibodies directed against several nuclear antigens. Coagulation studies revealed lupus anticoagulant. Echocardiography demonstrated reduced ejection fraction and moderate to severe mitral and tricuspid regurgitation. The patient was diagnosed with CAPS with hemorrhagic manifestations in the setting of new-onset SLE. The patient was treated with hemodialysis, high-dose glucocorticoids, plasma exchange, intravenous cyclophosphamide, and rituximab. Over the ensuing four weeks, the combination therapy led to hematological, cardiopulmonary, and renal recovery. This exceedingly rare case emphasizes that hemorrhagic manifestations, severe microangiopathic hemolytic anemia, and profound thrombocytopenia can dominate the clinical picture in CAPS.

Idiopathic myelofibrosis mimicking hemolytic anemia

Idiopathic Myelofibrosis is an infrequent chronic myeloproliferative disorder characterized by varying degrees of bone marrow fibrosis and extra medullary hematopoiesis, with the fibrosis being a reactive phenomenon to a neoplastic proliferation of a pluripotent hematopoietic stem cell. Idiopathic Myelofibrosis is heterogeneous in presentation and clinical course, with anemia being one of the most important problems. We present a case of a 59 year old male who presented with severe anemia, the peripheral blood picture mimicking hemolysis with numerous schistocytes and teardrop cells.Journal of Pathology of Nepal (2012) Vol. 2, 323-327DOI: http://dx.doi.org/10.3126/jpn.v2i4.6888

Moxifloxacin (Avelox) Induced Thrombotic Thrombocytopenic Purpura

We report a case of a 66-year-old African-American female who presented with complaints of progressively worsening weakness, shortness of breath on minimal exertion, lethargy for the last few days, and short episodes of aphasia lasting 20–30 seconds. Prior to presentation, she was treated with two courses of moxifloxacin for sinusitis. Laboratory examination was remarkable for anemia and thrombocytopenia with elevated lactate dehydrogenase and no evidence of renal failure. Peripheral smear showed numerous schistocytes and she was diagnosed with thrombotic thrombocytopenic purpura. Moxifloxacin was identified as the offending agent. The patient was treated with prednisone and plasmapheresis. To the best of our knowledge, this is the first reported case of thrombotic thrombocytopenic purpura associated with the use of moxifloxacin. Although rare, physicians should be aware of this serious complication associated with its use.

Acute renal failure and severe rhabdomyolysis in a patient with resistant thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder. This paper describes the case of a 39-year-old Sudanese male who presented to the emergency room with fever, jaundice, decreased level of consciousness, and worsening kidney function for 7 days, a high lactate dehydrogenase level (1947), severe thrombocytopenia (platelets 8), and numerous schistocytes in the peripheral blood smear. The patient was admitted with a diagnosis of TTP for plasma exchange. Fourteen days later, his creatinine kinase (CK) level rose to >50,000 IU; rhabdomyolysis was suggested. Continuous venovenous hemodialysis (CVVHD) was started. The patient’s CK level remained high, despite CVVHD, until the 6th day, after which this parameter gradually started to decrease. This report highlights a resistant case of TTP that presented with concomitant severe rhabdomyolysis, which demanded aggressive, continuous intervention.

Pseudo-thrombotic thrombocytopenic purpura: A rare presentation of pernicious anemia

Schistocytes are fragmented red blood cells due to the flow of blood through damaged capillaries and indicate endothelial injury. They are typical of microangiopathic hemolytic anemia seen in life threatening conditions like disseminated intravascular coagulation or thrombotic thrombocytopenic purpura/hemolytic uremic syndrome .We report a rare sub-acute presentation of pernicious anemia with hemolysis, thrombocytopenia and numerous schistocytes that was initially diagnosed as a more serious thrombotic thrombocytopenic purpura.A 31-year-old Caucasian woman presented with fatigue and paresthesia of both feet for 1 week. Past medical history included hypertension and gastro-esophageal reflux disease. Examination revealed scleral icterus and pallor. Examination of the abdomen did not show hepatosplenomegaly. Initial laboratory tests showed severe anemia, and low platelets. Indirect bilirubin and serum Lactate De Hydrogenase were elevated. Prothrombin time, partial thromboplastin time, serum fibrinogen, and serum fibrin degradation product levels were normal. Peripheral smear revealed numerous schistocytes, anisocytosis and macro-ovalocytes. Thrombotic thrombocytopenic purpura (TTP) was suspected due to the constellation of sub-acute onset of fatigue and paresthesia along with thrombocytopenia, schistocytes and an elevated LDH. Plasmapheresis was initiated for possible TTP. However, platelet count worsened despite plasmapheresis for 4 days. On re-evaluation, vitamin B(12) was found to be low. Treatment with intra-muscular vitamin B(12) led to symptomatic and hematologic improvement. Pernicious anemia was confirmed by the presence of anti-intrinsic factor antibodies, elevated serum gastrin level and atrophic gastritis.Clinicians must be aware of unusual clinical presentation of vitamin B(12) deficiency with schistocytes as the management is simple and effective.

Thrombotic thrombocytopenic purpura in the first trimester and successful pregnancy

Dear Editor, Thrombotic thrombocytopenic purpura (TTP) is a rare complication of pregnancy with a poor prognosis and a high fetal mortality when presenting early during gestation. Few cases of TTP (10%) occur during the first trimester [1, 2], the majority occurring at the time of delivery or during post-partum period [4, 6]. Until the effectiveness of plasma infusion and plasma exchange was recognized, TTP was associated with a mortality rate of 95% and, in case of pregnancy-related TTP, the maternal survival was rare and the fetal mortality rate approached 80% [9]. Fetal death is secondary to placental infarction due to thrombotic occlusion of the decidual arterioles [8]. Currently, plasma infusion and plasmapheresis have improved maternal and fetal survival rates [10]. At present, it is well known that termination of pregnancy is rarely needed and that the fetal survival rate could be improved by effective maternal therapy [14]. When TTP occurs during the first trimester of pregnancy and delivery of a viable infant is not an option, plasma exchange treatment is urgently indicated and may allow the pregnancy to continue [13]. There are some reports showing that prolonged courses of plasma exchange, beginning as early as 6 weeks of gestation, may achieve and maintain a remission of TTP allowing delivery of a healthy, full-term infant [1]. When plasma exchange fails to induce remission, therapeutic abortion may be considered, although the response of TTP to termination of pregnancy is uncertain. We have previously reported a case of a successful pregnancy in a young female who developed a severe TTP relapse at 18 weeks of gestation [5]. In the present study, we describe a case of a first pregnancy concomitant to a severe TTP diagnosed in the first trimester with maternal survival and delivery of a healthy child. In August 2004, a 26-year-old nulliparous woman at 9 weeks of gestation presenting macrohematuria and ecchymoses was admitted to our institution. Laboratory data showed thrombotic microangiopathy, with anemia (7.5 g/dl), thrombocytopenia (platelets 6×10/l), numerous schistocytes (60%) in the peripheral blood smears, elevated levels of lactic dehydrogenase (1,472 IU/l range 70–190) and bilirubin (total 3.4 mg/dl, normal value 0.4–1.1, indirect 3 mg/dl, normal value 0.1–0.4), reticulocytosis (250×10/l), and negative direct/indirect Coombs’ test. Renal function was normal. Bone marrow aspirate showed a normal bone marrow cytomorphology. Thrombophilic screening showed normal levels of antithrombin (AT), absence of lupus anticoagulant (LAC), normal levels of C and S proteins, and no mutations of Leiden Factor V and prothrombin gene, while a heterozygous mutation of MTHFR C677T, with normal plasma homocysteine concentrations, was found. Serologic examinations were negative for anti-extractable nuclear antibodies and anticardiolipin antibodies. Unfortunately, ADAMTS-13 levels and inhibitor were not determined during the acute event. On the basis of the symptoms and laboratory tests, a clinical diagnosis of TTP was made and the patient was treated with intravenous methylprednisolone (2 mg/kg/die to 120 mg/die) and daily plasmapheresis, with plasma replacement of 30 ml/kg/die, in combination with continuous infusion of fresh frozen plasma (FFP) (10 ml/kg/die). Folic acid (15 mg/die) support was given. The initial response was Ann Hematol (2009) 88:287–289 DOI 10.1007/s00277-008-0579-4

Infection in Renal Transplantation: A Case of Acute Q Fever

Acute Q fever is a zoonotic infection that most often occurs as an asymptomatic or very mild febrile illness. A small percentage of patients go on to develop chronic Q fever months or even years after the acute infection. We present a case of acute Q fever occurring in a renal transplant recipient who developed severe systemic disease with renal involvement. Serological diagnosis was carried out, and the patient was treated successfully with antibiotic therapy. This case emphasizes Q fever as one of the atypical infectious agents that may have serious consequences in immunocompromised renal transplant recipients and reminds us of the importance of careful inquiry regarding personal or occupational activities that could lead to exposure to specific organisms.

Fragmentation hemolytic anemia 8 years after replacement of ascending aorta with a sutureless intraluminal graft

A 56-year-old man underwent replacement of the ascending aorta with a sutureless intraluminal graft, for a Stanford type A aortic dissection. Eight years after the operation, he developed gross hemoglobinuria, associated with an intravascular hemolytic anemia. Due to numerous schistocytes in the peripheral blood, the hemolysis was attributed to mechanical injury of the red blood cells at the site of the vascular graft. The patient's course was complicated by an infection of the aortic graft, which led to an urgent graft replacement. The hemolytic anemia resolved completely shortly after the reoperation. Physicians should consider this etiology in the differential diagnosis of fragmentation hemolytic anemia.

Red Cell Changes in Top, Middle and Bottom Layer of Packed Red Cells in Vitamin B12 Deficiency

Surviving macroreticulocytes are released to peripheral blood during the first 4 d following a B12 injection to vitamin B12 deficient patients with grave anaemia. Marked increase in number of reticulocytes, together with corresponding reduction in reticulocyte size is noted in the top layer of the centrifuged packed red column from d 4 to 6 after medication. This 'remodelling' of the 'stress-reticulocytes' seems best explained by a division of the cells into 2 equal, surviving, normal-sized reticulocytes. The macroreticulocytes, which probably result from skipped division in the marrow, may thus complete their last cytoplasmatic division in the peripheral blood. The numerous schistocytes, which are found in the top layer of the centrifuged packed red cell column, disappear during the first few days after treatment, and it is assumed that these cells are fragments from the relatively few megalocytes which have reached the peripheral blood prior to medication. Macroreticulocytes seem to have a maximum deformability on d 5 after the B12 injection, shortly after the cell division has started.