Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome and Disseminated Intravascular Coagulation

Thrombocytopenia-associated multiple organ failure (TAMOF) is a clinical syndrome often managed by critical care physicians. It is characterized by new onset thrombocytopenia in the setting of evolving multiple organ failure. TAMOF is an entity within the family of thrombotic microangiopathies, a spectrum of mixed coagulopathies and thrombotic disorders that include thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) on one end of the spectrum and disseminated intravascular coagulation (DIC) on the other. Autopsies performed in patients who have succumbed to DIC, TTP and HUS reveal disseminated microvascular thromboses with distinct findings that help to differentiate these three entities. Furthermore, our biologic and molecular understanding of the pathophysiologic processes governing DIC, TTP and HUS have significantly expanded and allow better laboratory delineation among these three entities. Tissue factor plays a pivotal role in the initiation and propagation of DIC. Von Willebrand factors and deficient ADAMTS-13 (a.k.a von Willebrand factor-cleaving proteinase) drive the pathology in TTP. Shiga toxins and the complement pathway drive the pathology in HUS. With better understanding of the biology of TAMOF syndrome, innovative therapies are currently being evaluated with the hope of reversing this destructive pathology.

Fas, a member of the tumor necrosis receptor superfamily, is 36 kD surface protein containing a single transmembrane region and induces apoptosis by Fas-Fas ligand binding. Soluble Fas (sFas) is produced as the form lacking 21 amino acid residues containing the transmembrane domain by alternative splicing. We found that the plasma sFas levels of 33 patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), 19 patients with disseminated intravascular coagulation (DIC), and 10 non-DIC patients with multiple organ failure (MOF) were significantly higher than those of 21 non-DIC patients without organ failure and those of 25 healthy volunteers. The plasma sFas ligand levels of the TTP/HUS patients, the DIC patients, and the non-DIC patients with MOF were significantly higher than those of the non-DIC patients without organ failure and those of the healthy volunteers. The plasma sFas levels were significantly correlated with the plasma sFas ligand levels in all subjects. The plasma thrombomodulin (TM) levels were increased significantly in the TTP/HUS patients, the DIC patients, and the non-DIC patients with MOF compared with the levels of the non-DIC patients without organ failure and the healthy volunteers. The plasma sFas antigen levels were correlated significantly with the plasma TM levels in all subjects. These findings suggest that the increases of sFas and sFas ligand that cause apoptosis might be related to the vascular endothelial cell injuries in TTP and DIC with organ failure.

Thrombocytopenia-Associated Multiple Organ Failure and Acute Kidney Injury

Schistocytes on the Peripheral Blood Smear

Improving Residents' Knowledge of Peripheral Smears

This chapter discusses the diagnosis, evaluation and management of gastrointestinal bleeding including upper gastrointestinal bleeding (UGIB) and lower gastrointestinal bleeding (LGIB). It describes the special circumstances with regard to aortoenteric fistula, liver disease, and Jehovah's Witnesses. In UGIB, patients typically present with hematemesis, coffee-ground emesis, and/or melena. In LGIB, patients typically present with bright red blood per rectum (BRBPR), also known as hematochezia. Higher severity of disease is indicated by signs of shock such as hypotension, tachycardia, altered mental status (AMS), decreased urine output (UOP), cool skin, syncope, orthostasis. Change in pulse with posture is more sensitive than hypotension, but may be masked by medications (e.g., beta-blockers). Hypotension, tachycardia, and tachypnea can indicate hemorrhagic shock and requires immediate treatment. Massive transfusion protocols are helpful for significant bleeding in order to prevent further coagulopathy due to transfusion of high volume of crystalloid or only red cells.

BackgroundThrombotic microangiopathies (TMAs) occurring in the postpartum period may be difficult to manage. They present as the combination of mechanical hemolytic anemia and consumption thrombocytopenia due to endothelial dysfunction. The cause of this endothelial aggression can be multiple: thrombocytopenic thrombotic purpura (TTP), HELLP syndrome, antiphospholipid syndrome, atypical hemolytic and uremic syndrome or acute fatty liver of pregnancy. TTP results from a severe deficiency of ADAMTS13, which is a protease cleaving specifically von Willebrand factor chiefly produced by liver cells. There are two main causes, the production of anti-ADAMTS13 auto-antibodies and, more rarely, a genetic deficiency in ADAMTS13. First-line treatment is based on plasma exchange. HELLP syndrome occurs in the third trimester of pregnancy usually in association with preeclampsia and represents a form of TMA characterized by damage to the sinusoidal capillaries of the liver. Prompt delivery is the main treatment. We present a case illustrating the challenges in discriminating between different postpartum TMAs, with a focus on the distinction between TTP and HELLP syndrome. Specifically, we highlight how acute liver failure (ALF) stemming from HELLP may lead to TTP with a spectacular response to plasma exchanges.CaseA 28-year-old, 33 + 4 weeks pregnant woman presented with severe preeclampsia complicated by ALF in the setting of partial liver necrosis, disseminated intravascular coagulation, microangiopathic hemolytic anemia and acute kidney injury. Greatly diminished levels of ADAMTS13 (< 5%) activity and neurological impairment suggested an initial diagnosis of thrombotic thrombocytopenic purpura (TTP). Therapeutic plasma exchange (TPE) was initiated and complete renal, neurological, hematological and hepatic recovery was observed. Secondary TTP induced by ALF due to HELLP syndrome was the final diagnosis.ConclusionOur case addresses the overlapping nature of postpartum TMAs and raises the possibility that HELLP-induced ALF may constitute an additional mechanism resulting in TTP, thereby opening a possible indication for TPE.

PURPOSE: To discuss the current rationale for the use of specific and nonspecific therapies for thrombotic microangiopathy in thrombocytopenia-associated pediatric multiple organ failure syndromes. Methods: Pertinent PubMed and MEDLINE citations and proceedings of recent critical care meeting presentations were reviewed. RESULTS: Critical care clinicians have reported using antithrombin III concentrate, protein C concentrate, activated protein C, prostacyclin and its analogues, heparin, tissue factor pathway inhibitor concentrate, plasma infusion, plasma exchange, whole blood exchange, pentoxifylline, tissue plasminogen activator, urokinase, and streptokinase with perceived therapeutic benefits in patients with thrombocytopenia-associated multiple organ failure, including those with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation syndrome, and secondary thrombotic microangiopathy syndrome without prolonged prothrombin time/activated partial thromboplastin time. CONCLUSION: Assuming that underlying disease is remediable, a consensus has developed that thrombotic microangiopathy is a therapeutic target in children with thrombocytopenia-associated multiple organ failure syndromes. Studies are warranted to delineate efficacious use of specific and nonspecific therapies to prevent and reverse thrombotic microangiopathy in these patients.

The spectrum of kidney disease occurring during pregnancy includes preeclampsia, hypertensive disorders of pregnancy, urinary tract infection, acute kidney injury, and renal cortical necrosis (RCN). Preeclampsia affects approximately 3–5% of pregnancies. We observed preeclampsia in 5.8% of pregnancies, and 2.38% of our preeclamptic women developed eclampsia. Severe preeclampsia and the eclampsia or hemolysis, elevated liver enzymes levels, and low platelets count (HELLP) syndrome accounted for about 40% of cases of acute kidney injury (AKI) in pregnancy. Preeclampsia/eclampsia was the cause of acute renal failure (ARF) in 38.3% of the cases. Preeclampsia was the most common (91.7%) cause of hypertension during pregnancy, and chronic hypertension was present in 8.3% of patients. We observed urinary tract infection (UTI) in 9% of pregnancies. Sepsis resulting from pyelonephritis can progress to endotoxic shock, disseminated intravascular coagulation, and AKI. The incidence of premature delivery and low birth weight is higher in women with UTI. The incidence of AKI in pregnancy with respect to total ARF cases has decreased over the last 30 years from 25% in 1980s to 5% in 2000s. Septic abortion-related ARF decreased from 9% to 3%. Prevention of unwanted pregnancy and avoidance of septic abortion are key to eliminate abortion-associated ARF in early pregnancy. The two most common causes of ARF in third trimester and postpartum periods were puerperal sepsis and preeclampsia/HELLP syndrome. Pregnancy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and acute fatty liver of pregnancy were rare causes of ARF. Despite decreasing incidence, AKI remains a serious complication during pregnancy.

Thrombopénie et grossesse : du diagnostic étiologique à la prise en charge thérapeutique

The article presents the results of studies of changes in the shape of red blood cells during spontaneous babesiosis in dogs. It was found that in 2019, seasonal outbreaks are caused and characterized by the presence of two waves – spring-summer with a peak in June and autumn with a peak in October. The intensity of parasitemia increases synchronously with the extensity of infestation in the first half of the year(a narrow direct correlation), in the future it falls and does not correlate with outbreaks of animal disease. Clinically, the spring-summer wave of the disease is characterized by an acute-subacute typical course with pronounced classic clinical signs. The autumn wave had a predominantly subacute-atypical course, with the development of severe complications with signs of hepatopathy and acute renal insufficiency, cardiomyopathy and myocarditis, lesions of the nervous system, the development of shock with a significant tendency to decompensation. Changes in the shape of red blood cells are bright and indicative markers of the state of animals on babesiosis. Poikilocytosis was detected in 92.3 % of sick dogs. The most common changes are acanthocytosis and vacuolization of erythrocytes (irreversible forms), which qualitatively assess the degree of damage to vital organs. Echinocytes are reversible forms that appear in the early stages and determine the development of renal and hepatic pathologies. Stomatocytes accompany the development of inflammatory and dystrophic pathologies, qualitatively characterize the degree of hemolytic anemia. Their intensity is synchronous with the extent of the invasion. The appearance of schizocytes is a formidable symptom that is pathognomonic for disseminated intravascular coagulation syndrome. This marker requires immediate use of intensive care. The assessment of qualitative changes in the form of red blood cells, the calculation of the intensity of erythrocyte lesions allows you to determine the severity of the condition of the body of sick dogs, the degree of metabolic disorders, hemolytic anemia, hepatopathy, the severity of intoxication, uremic syndrome, spleen hyperplasia, as well as identify the development of DIC syndrome, kidney failure and “shock kidney”. Such an assessment is necessary for making timely and adequate decisions regarding therapeutic measures for spontaneous babesiosis of dogs.

Thrombocytopenia in cancer patients