Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT).

No lab test can reliably predict if neonatal thrombocytopenia will occur. The risk of neonatal thrombocytopenia is increased with:

- Mothers with a history of splenectomy for ITP

- Mothers who had a previous infant affected with ITP

- Gestational (maternal) platelet count less than 100,000/uL

It is recommended that pregnant women with thrombocytopenia or a previous diagnosis of ITP should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. It is recommended that neonates be followed with serial platelet counts for the first few days after birth.,

A normal platelet count is considered to be in the range of 150,000–450,000 per microlitre (μl) of blood for most healthy individuals. Hence one may be considered thrombocytopenic below that range, although the threshold for a diagnosis of ITP is not tied to any specific number.

The incidence of ITP is estimated at 50–100 new cases per million per year, with children accounting for half of that amount. At least 70 percent of childhood cases will end up in remission within six months, even without treatment. Moreover, a third of the remaining chronic cases will usually remit during follow-up observation, and another third will end up with only mild thrombocytopenia (defined as a platelet count above 50,000). A number of immune related genes and polymorphisms have been identified as influencing predisposition to ITP, with FCGR3a-V158 allele and KIRDS2/DL2 increasing susceptibility and KIR2DS5 shown to be protective.

ITP is usually chronic in adults and the probability of durable remission is 20–40 percent. The male to female ratio in the adult group varies from 1:1.2 to 1.7 in most age ranges (childhood cases are roughly equal for both genders) and the median age of adults at the diagnosis is 56–60. The ratio between male and female adult cases tends to widen with age. In the United States, the adult chronic population is thought to be approximately 60,000—with women outnumbering men approximately 2 to 1, which has resulted in ITP being designated an orphan disease.

The mortality rate due to chronic ITP varies but tends to be higher relative to the general population for any age range. In a study conducted in Great Britain, it was noted that ITP causes an approximately 60 percent higher rate of mortality compared to gender- and age-matched subjects without ITP. This increased risk of death with ITP is largely concentrated in the middle-aged and elderly. Ninety-six percent of reported ITP-related deaths were individuals 45 years or older. No significant difference was noted in the rate of survival between males and females.

Thrombocytopenia affects a few percent of newborns, and its prevalence in neonatal intensive care units (NICU) is high. Normally, it is mild and resolves without consequences. Most cases affect preterm birth infants and result from placental insufficiency and/or fetal hypoxia. Other causes, such as alloimmunity, genetics, autoimmunity, and infection, are less frequent.

Thrombocytopenia that starts after the first 72 hours since birth is often the result of underlying sepsis or necrotizing enterocolitis (NEC). In the case of infection, PCR tests may be useful for rapid pathogen identification and detection of antibiotic resistance genes. Possible pathogens include viruses (e.g. Cytomegalovirus (CMV), rubella virus, HIV), bacteria (e.g. "Staphylococcus sp.", "Enterococcus sp.", "Streptococcus agalactiae" (GBS), "Listeria monocytogenes", "Escherichia coli", "Haemophilus influenzae", "Klebsiella pneumoniae", "Pseudomonas aeruginosa", "Yersinia enterocolitica"), fungi (e.g. "Candida sp."), and "Toxoplasma gondii". The severity of thrombocytopenia may be correlated with pathogen type; some research indicates that the most severe cases are related to fungal or gram-negative bacterial infection. The pathogen may be transmitted during or before birth, by breast feeding, or during transfusion. Interleukin-11 is being investigated as a drug for managing thrombocytopenia, especially in cases of sepsis or necrotizing enterocolitis (NEC).

Abnormally high rates of platelet destruction may be due to immune or non-immune conditions, including:

- Immune thrombocytopenic purpura

- Thrombotic thrombocytopenic purpura

- Hemolytic-uremic syndrome

- Disseminated intravascular coagulation

- Paroxysmal nocturnal hemoglobinuria

- Antiphospholipid syndrome

- Systemic lupus erythematosus

- Post-transfusion purpura

- Neonatal alloimmune thrombocytopenia

- Hypersplenism

- Dengue fever

- Gaucher's disease

- Zika virus

The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for patients with idiopathic TTP diagnosed and treated early with plasmapheresis.

Secondary TTP is diagnosed when the patient's history mentions one of the known features associated with TTP. It comprises about 40% of all cases of TTP. Predisposing factors are:

- Cancer

- Bone marrow transplantation

- Pregnancy

- Medication use:

- Antiviral drugs (acyclovir)

- Certain chemotherapy medications such as gemcitabine and mitomycin C

- Quinine

- Oxymorphone

- Quetiapine

- Bevacizumab

- Sunitinib

- Platelet aggregation inhibitors (ticlopidine, clopidogrel, and prasugrel)

- Immunosuppressants (ciclosporin, mitomycin, tacrolimus/FK506, interferon-α)

- Hormone altering drugs (estrogens, contraceptives, hormone replacement therapy)

- HIV-1 infection

The mechanism of secondary TTP is poorly understood, as ADAMTS13 activity is generally not as depressed as in idiopathic TTP, and inhibitors cannot be detected. Probable etiology may involve, at least in some cases, endothelial damage, although the formation of thrombi resulting in vessel occlusion may not be essential in the pathogenesis of secondary TTP. These factors may also be considered a form of secondary aHUS; patients presenting with these features are, therefore, potential candidates for anticomplement therapy.

Evans syndrome is rare, serious, and has a reported mortality rate of 7%.

It has been observed that there is a risk of developing other autoimmune problems and hypogammaglobulinemia, with recent research finding that 58% of children with Evans syndrome have CD4-/CD8- T cells which is a strong predictor for having autoimmune lymphoproliferative syndrome.

Diagnosis is done by the help of symptoms and only blood count abnormality is thrombocytopenia.

By tradition, the term idiopathic thrombocytopenic purpura is used when the cause is idiopathic. However, most cases are now considered to be immune-mediated.

Another form is thrombotic thrombocytopenic purpura.

aHUS can be inherited or acquired, and does not appear to vary by race, gender, or geographic area. As expected with an ultra-rare disease, data on the prevalence of aHUS are extremely limited. A pediatric prevalence of 3.3 cases per million population is documented in one publication of a European hemolytic uremic syndrome (HUS) registry involving 167 pediatric patients.

Immune thrombocytopenic purpura (), sometimes called idiopathic thrombocytopenic purpura is a condition in which autoantibodies are directed against a patient's own platelets, causing platelet destruction and thrombocytopenia. Anti-platelet autoantibodies in a pregnant woman with immune thrombocytopenic purpura will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by will have platelet counts <50,000 μL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with .

Mothers with thrombocytopenia or a previous diagnosis of should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their which may include steroids or . Fetal blood analysis to determine the platelet count is not generally performed as -induced thrombocytopenia in the fetus is generally less severe than . Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia.

Onyalai is limited to black populations in central southern Africa. The affected age range is from less than a year to 70 years and seems not to be gender-specific in the same manner as ITP. Cases generally peak between 11 and 20 years old.

Analysis of patient admissions in Namibia between 1981 and 1988 showed an incidence rate of onyalai to be 1.19% with the annual incidence varying between 0.96% and 1.66% of all admissions. The female to male ratio was 3:2. The mean age at presentation was 24.8 years (range 6 months to 80 years) and the mean hospital stay (and duration of clinical bleeding) was 7.68 days (ranging between 1–38 days). The treatment policy of commencing intravenous fluid on admission and a blood transfusion whenever the haemoglobin dropped below 10 g/dl in patients with active bleeding was associated with a mortality rate of 2.78% compared to 9.8% in cases recorded up to 1981.

The most rapidly effective treatment in infants with severe hemorrhage and/or severe thrombocytopenia (30,000 μL) an infusion of (1 g/kg/day for two days) in the infant has been shown to rapidly increase platelet count and reduce the risk of related injury.

After a first affected pregnancy, if a mother has plans for a subsequent pregnancy, then the mother and father should be typed for platelet antigens and the mother screened for alloantibodies. Testing is available through reference laboratories (such as ). testing of the father can be used to determine zygosiity of the involved antigen and therefore risk to future pregnancies (if homozygous for the antigen, all subsequent pregnancies will be affected, if heterozygous, there is an approximate 50% risk to each subsequent pregnancy). During subsequent pregnancies, the genotype of the fetus can also be determined using amniotic fluid analysis or maternal blood as early as 18 weeks gestation to definitively determine the risk to the fetus.

Considered a rare to very rare autoimmune disorder it has had few studies with cohorts often less than 30.

Patients with aHUS have an extremely poor prognosis. Among those with the most commonly identified aHUS genetic mutation, the proportion of patients experiencing negative outcomes (e.g., need for dialysis, permanent kidney damage, death) within the first year rises to 70%. However, sudden morbidity and mortality can occur regardless of mutational status. aHUS can arise at any age, with more than 40% of cases first reported after 18 years of age. The oldest presentation in one study was at age 83. As noted above, kidney transplantation for aHUS patients with ESRD was rarely considered because of a high incidence of graft loss due to TMA recurrence in the transplanted organ in up to 90% of patients. Consequently, most aHUS patients with ESRD undergo chronic dialysis, which is associated with significant morbidities and worsened prognosis. Combined liver-kidney transplantation has been attempted in patients with aHUS, although this high-risk procedure has a mortality rate approaching 50%.

Quality of life is very poor for patients with aHUS, who are burdened with fatigue, renal complications, hypertension, neurological impairment, gastrointestinal distress, clotting at the site of venous access, and ultimately, death. PE/PI is also reported to be associated with significant safety risks and is highly disruptive to patients’ lives due to the requirements for extensive vascular access and frequent administration.

Cryoglobulonemia may occur without evidence of an underlying associated disorders, i.e. primary cryoglobulinemia (also termed essential cryoglobulinemia) or, far more commonly, with evidence of an underlying disease, i.e. secondary cryoglobulonemia. Secondary cryofibrinoenemia can develop in individuals suffering infection (~12% of cases), malignant or premalignant disorders (21%), vasculitis (25%), and autoimmune diseases (42%). In these cases of the secondary disorder, cryofibinogenema may or may not cause tissue injury and/or other symptoms and the actual cause-effect relationship between these diseases and the development of cryofibrinogenmia is unclear. Cryofibrinogenemia can also occur in association with the intake of certain drugs.

The occurrence of cryofibrinogenemia as defined by a 4 °C-induced formation of fibrinogen-based precipitation in plasma occurs in 2% to 9% of asymptomatic individuals and 8% to 13% of hospitalized patients without symptoms attributable to this precipitation. Most of these cases have relatively low levels of cold temperature-induced fibrinogen precipitate levels (<50 milligram/liter of fibrinogen) and do not have a disorder associated with the development of cryofibrinogenmia.

The amount of fresh frozen plasma required to reverse disseminated intravascular coagulation associated with purpura fulminans may lead to complications of fluid overload and death, especially in neonates, such as transfusion-related acute lung injury. Exposure to multiple plasma donors over time increases the cumulative risk for transfusion-associated viral infection and allergic reaction to donor proteins found in fresh frozen plasma.

Allergic reactions and alloantibody formation are also potential complications, as with any protein replacement therapy.

Concomitant warfarin therapy in subjects with congenital protein C deficiency is associated with an increased risk of warfarin skin necrosis.

Inadequate nutrition or the consumption of tainted food are suspected. Both IgG and IgM autoantibodies to platelet and to glycoprotein IIb/IIIa is found in majority of patients.

Purpura fulminans is rare and most commonly occurs in babies and small children but can also be a rare manifestation in adults when it is associated with severe infections. For example, Meningococcal septicaemia is complicated by purpura fulminans in 10–20% of cases among children. Purpura fulminans associated with congenital (inherited) protein C deficiency occurs in 1:500,000–1,000,000 live births.

In diseases such as hemolytic uremic syndrome, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and malignant hypertension, the endothelial layer of small vessels is damaged with resulting fibrin deposition and platelet aggregation. As red blood cells travel through these damaged vessels, they are fragmented resulting in intravascular hemolysis. The resulting schistocytes (red cell fragments) are also increasingly targeted for destruction by the reticuloendothelial system in the spleen, due to their narrow passage through obstructed vessel lumina. It is seen in systemic lupus erythematosus, where immune complexes aggregate with platelets, forming intravascular thrombi. Microangiopathic hemolytic anemia is also seen in cancer.

Automated analysers (the machines that perform routine full blood counts in most hospitals) are generally programmed to flag blood films that display red blood cell fragments or "schistocytes".

Purpura are a common and nonspecific medical sign; however, the underlying mechanism commonly involves one of:

- Platelet disorders (thrombocytopenic purpura)

- Primary thrombocytopenic purpura

- Secondary thrombocytopenic purpura

- Post-transfusion purpura

- Vascular disorders (nonthrombocytopenic purpura)

- Microvascular injury, as seen in senile (old age) purpura, when blood vessels are more easily damaged

- Hypertensive states

- Deficient vascular support

- Vasculitis, as in the case of Henoch–Schönlein purpura

- Coagulation disorders

- Disseminated intravascular coagulation (DIC)

- Scurvy (vitamin C deficiency) - defect in collagen synthesis due to lack of hydroxylation of procollagen results in weakened capillary walls and cells

- Meningococcemia

- Cocaine use with concomitant use of the one-time chemotherapy drug and now veterinary deworming agent levamisole can cause purpura of the ears, face, trunk, or extremities, sometimes needing reconstructive surgery. Levamisole is purportedly a common cutting agent.

- Decomposition of blood vessels including purpura is a symptom of acute radiation poisoning in excess of 2 Grays of radiation exposure. This is an uncommon cause in general, but is commonly seen in victims of nuclear disaster.

Cases of psychogenic purpura are also described in the medical literature, some claimed to be due to "autoerythrocyte sensitization". Other studies suggest the local (cutaneous) activity of tissue plasminogen activator can be increased in psychogenic purpura, leading to substantial amounts of localized plasmin activity, rapid degradation of fibrin clots, and resultant bleeding. Petechial rash is also characteristic of a rickettsial infection.

The specific cause is dependent of the type of TMA that is presented, but the two main pathways that lead to TMA are external triggers of vascular injury, such as viruses, bacterial Shiga toxins or endotoxins, antibodies, and drugs; and congenital predisposing conditions, including decreased levels of tissue factors necessary for the coagulation cascade. Either of these pathways will result in decreased endothelial thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, enhanced vascular shear stress, and abnormal vWF fragmentation. The central and primary event in this progression is injury to the endothelial cells, which reduces the production of prostaglandin and prostacyclin, ultimately resulting in the loss of physiological thromboresistance, or high thrombus formation rate in blood vessels. Leukocyte adhesion to the damaged endothelial wall and abnormal von Willebrand factor (or vWF) release can also contribute to the increase in thrombus formation. More recently, researchers have attributed both TTP and HUS to targeted agents, such as targeted cancer therapies, immunotoxins, and anti-VEGF therapy.

Bacterial toxins are the primary cause of one category of thrombotic microangiopathy known as HUS or hemolytic uremic syndrome. HUS can be divided into two main categories: Shiga-toxin-associated HUS (STx-HUS), which normally presents with diarrhea, and atypical HUS. The Shiga-toxin inhibits the binding of eEF-1-dependent binding of aminoacyl tRNA to the 60S subunit of the ribosome, thus inhibiting protein synthesis. The cytotoxicity from the lack of protein damages glomerular endothelial cells by creating voids in the endothelial wall and detaching the basement membrane of the endothelial layer, activating the coagulation cascade. Atypical HUS may be caused by an infection or diarrheal illness or it may be genetically transmitted. This category of TMA encompasses all forms that do not have obvious etiologies. Mutations in three of the proteins in the complement cascade have been identified in patients with atypical HUS. Several chemotherapeutic drugs have also been shown to cause damage to the epithelial layer by reducing the ability for the cells to produce prostacyclin, ultimately resulting in chemotherapy-associated HUS, or C-HUS.

The second category of TMAs is TTP thrombotic thrombocytopenic purpura, which can be divided into 3 categories: congenital, idiopathic, and non-idiopathic. Congenital and idiopathic TTP are generally associated with deficiencies in ADAMTS13, a zinc metalloprotease responsible for cleaving Very Large vWF Multimers in order to prevent inappropriate platelet aggregation and thrombosis in the microvasculature. Natural genetic mutations resulting in the deficiency of ADAMTS13 have been found in homozygous and heterozygous pedigrees in Europe. Researchers have identified common pathways and links between TTP and HUS, while other sources express skepticism about their common pathophysiology.

The repression of the vascular endothelial growth factor (VEGF) can also cause glomerular TMA (damage to the glomerular microvasculature). It is likely that the absence of VEGF results in the collapse of fenestrations in the glomerular endothelium, thus causing microvascular injury and blockages associated with TMA.

Manifestations resembling thrombotic microangiopathy have been reported in clinical trials evaluating high doses of Valacyclovir (8000 mg/day) administered for prolonged periods (months to years) for prophylaxis of cytomegalovirus (CMV) infection and disease, particularly in persons with HIV infection. A number of factors may have contributed to the incidence of thrombotic microangiopathy in those trials including profound immunosuppression, underlying diseases (advanced HIV disease, graft-versus-host disease), and other classes of drug, particularly antifungal agents. There were no reports of thrombotic microangiopathy among the 3050 subjects in the four trials evaluating Valacyclovir for suppression of recurrent genital herpes. Although one of the trials was in HIV-infected subjects, the patients did not have advanced HIV disease. The implication is that the occurrence of thrombotic microangiopathy is restricted to severely immunosuppressed persons receiving higher Valacyclovir dosages than are required to control HSV infection.

In medicine (hematology) microangiopathic hemolytic anemia (MAHA) is a microangiopathic subgroup of hemolytic anemia (loss of red blood cells through destruction) caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.

Drug-induced purpura is a skin condition that may be related to platelet destruction, vessel fragility, interference with platelet function, or vasculitis.