The clinical presentation of TMA, although dependent on the type, typically includes: fever, microangiopathic hemolytic anemia (see schistocytes in a blood smear), renal failure, thrombocytopenia and neurological manifestations. Generally, renal complications are particularly predominant with Shiga-toxin-associated hemolytic uremic syndrome (STx-HUS) and atypical HUS, whereas neurologic complications are more likely with TTP. Individuals with milder forms of TTP may have recurrent symptomatic episodes, including seizures and vision loss. With more threatening cases of TMA, and also as the condition progresses without treatment, multi-organ failure or injury is also possible, as the hyaline thrombi can spread to and affect the brain, kidneys, heart, liver, and other major organs.

Thrombotic microangiopathy (TMA) is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury. It may be seen in association with thrombocytopenia, anemia, purpura and renal failure.

The classic TMAs are hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Other conditions with TMA include atypical hemolytic uremic syndrome, disseminated intravascular coagulation, scleroderma renal crisis, malignant hypertension,

antiphospholipid antibody syndrome, and drug toxicities, e.g. calcineurin inhibitor toxicity.

The signs and symptoms of TTP may at first be subtle and nonspecific. Many people experience an influenza-like or diarrheal illness before developing TTP. Neurological symptoms are very common and vary greatly in severity. Frequently reported symptoms include feeling very tired, confusion, and headaches. Seizures and symptoms similar to those of a stroke can also be seen.

As TTP progresses, blood clots form within small blood vessels (microvasculature), and platelets (clotting cells) are consumed. As a result, bruising, and rarely bleeding can occur. The bruising often takes the form of purpura, while the most common site of bleeding, if it occurs, is from the nose or gums. Larger bruises (ecchymoses) may also develop.

The classic presentation of TTP includes a constellation of five medical signs which classically support the clinical diagnosis of TTP, although it is unusual for patients to present with all 5 symptoms. The pentad includes:

- Fever

- Changes in mental status

- Thrombocytopenia

- Reduced kidney function

- Haemolytic anaemia (microangiopathic hemolytic anemia).

High blood pressure (hypertension) may be found on examination.

In DIC, the underlying cause usually leads to symptoms and signs, and DIC is discovered on laboratory testing. The onset of DIC can be sudden, as in endotoxic shock or amniotic fluid embolism, or it may be insidious and chronic, as in cancer. DIC can lead to multiorgan failure and widespread bleeding.

Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts of the body. As clotting factors and platelets are used up, bleeding may occur. This may include blood in the urine, blood in the stool, or bleeding into the skin. Complications may include organ failure.

Relatively common causes include sepsis, surgery, major trauma, cancer, and complications of pregnancy. Less common causes include snake bites, frostbite, and burns. There are two main types acute (rapid onset) and chronic (slow onset). Diagnosis is typically based on blood tests. Findings may include low platelets, low fibrinogen, high INR, or high D-dimer.

Treatment is mainly directed towards the underlying condition. Other measures may include giving platelets, cryoprecipitate, or fresh frozen plasma. Evidence to support these treatments, however, is poor. Heparin may be useful in the chronic form. About 1% of people admitted to hospital are affected by the condition. In those with sepsis rates are between 20% and 50%. The risk of death among those affected varies from 20 to 50%.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body, resulting in low platelet counts. These small blood clots, called thrombi, can damage many organs including the kidneys, heart, brain, and nervous system. In the era before effective treatment with plasma exchange, the fatality rate was about 90%. With plasma exchange, this has dropped to 10% at six months. Because the disease generally results from antibodies that activate the immune system to inhibit the ADAMTS13 enzyme, agents that suppress the immune system, such as glucocorticoids, rituximab, cyclophosphamide, vincristine, or ciclosporin, may also be used if a relapse or recurrence follows plasma exchange. Platelets are not transfused unless the patient has a life-threatening bleed, since the transfused platelets would also quickly be consumed by thrombi formation, leading to a minimal increase in circulating platelets.

Most cases of TTP arise from autoantibody-mediated inhibition of the enzyme ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand factor (vWF) into smaller units. The increase in circulating multimers of vWF increases platelet adhesion to areas of endothelial injury, particularly where arterioles and capillaries meet, which in turn results in the formation of small platelet clots called thrombi. As platelets are used up in the formation of thrombi, this then leads to a decrease in the number of overall circulating platelets, which may then cause life-threatening bleeds. The reason why the antibodies form is generally unknown for most patients, though it can be associated with some medications and autoimmune diseases such as HIV and Lupus, as well as pregnancy.

A rarer form of TTP, called Upshaw–Schulman syndrome, or "Inherited TTP," results from an autosomal recessive gene that leads to ADAMTS13 dysfunction from the time of birth, resulting in persisting large vWF multimers, which in turn results in the formation of thrombi (small platelet clots).

Red blood cells passing the microscopic clots are subjected to shear stress, which damages their membranes, leading to rupture of red blood cells within blood vessels, which in turn leads to anaemia and schistocyte formation. The presence of these blood clots in the small blood vessels reduces blood flow to organs resulting in cellular injury and end organ damage. Current therapy is based on support and plasmapheresis to reduce circulating antibodies against ADAMTS13 and replenish blood levels of the enzyme.

Clinical signs and symptoms of complement-mediated TMA can include abdominal pain, confusion, fatigue, edema (swelling), nausea/vomiting and diarrhea. aHUS often presents with malaise and fatigue, as well as microangiopathic anemia. However, severe abdominal pain and bloody diarrhea are unusual. Laboratory tests may also reveal low levels of platelets (cells in the blood that aid in clotting), elevated lactate dehydrogenase (LDH, a chemical released from damaged cells, and which is therefore a marker of cellular damage), decreased haptoglobin (indicative of the breakdown of red blood cells), anemia (low red blood cell count)/schistocytes (damaged red blood cells), elevated creatinine (indicative of kidney dysfunction), and proteinuria (indicative of kidney injury). Patients with aHUS often present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, or coma. Failure of neurologic, cardiac, kidney, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression. For example, approximately 1 in 6 patients with aHUS initially will present with proteinuria or hematuria without acute kidney failure. Patients who survive the presenting signs and symptoms endure a chronic thrombotic and inflammatory state, which puts many of them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death.

Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.

Early purpura fulminans lesions look similar to traumatic skin bleeds or purpuric rashes, such as immune thrombocytopenic purpura or thrombotic thrombocytopenic purpura; however, purpura fulminans will rapidly progress to necrosis whereas other purpuric rashes do not. In most cases, differential diagnoses may be distinguished from purpura fulminans by other clinical and laboratory findings.

The initial appearance of purpura fulminans lesions is of well-demarcated erythematous lesions which progress rapidly to develop irregular central areas of blue-black haemorrhagic necrosis. Advancing areas of necrosis are often surrounded by a thin border of erythema that fades into adjacent unaffected skin. Haemorrhage into the necrotic skin causes purpura fulminans lesions to become painful, dark and raised, sometimes with vesicle or blister (bulla) formation.

The distribution of purpura fulminans lesions may be different according to the underlying pathogenesis. Purpura fulminans in severe sepsis typically develops in the distal extremities and progresses proximally or appears as a generalised or diffuse rash affecting the whole body surface. In cases of severe inheritable protein C deficiency, purpura fulminans with disseminated intravascular coagulation manifests within a few hours or days after birth.

The most common conditions associated with thrombophilia are deep vein thrombosis (DVT) and pulmonary embolism (PE), which are referred to collectively as venous thromboembolism (VTE). DVT usually occurs in the legs, and is characterized by pain, swelling and redness of the limb. It may lead to long-term swelling and heaviness due to damage to valves in the veins. The clot may also break off and migrate (embolize) to arteries in the lungs. Depending on the size and the location of the clot, this may lead to sudden-onset shortness of breath, chest pain, palpitations and may be complicated by collapse, shock and cardiac arrest.

Venous thrombosis may also occur in more unusual places: in the veins of the brain, liver (portal vein thrombosis and hepatic vein thrombosis), mesenteric vein, kidney (renal vein thrombosis) and the veins of the arms. Whether thrombophilia also increases the risk of arterial thrombosis (which is the underlying cause of heart attacks and strokes) is less well established.

Thrombophilia has been linked to recurrent miscarriage, and possibly various complications of pregnancy such as intrauterine growth restriction, stillbirth, severe pre-eclampsia and abruptio placentae.

Protein C deficiency may cause purpura fulminans, a severe clotting disorder in the newborn that leads to both tissue death and bleeding into the skin and other organs. The condition has also been described in adults. Protein C and protein S deficiency have also been associated with an increased risk of skin necrosis on commencing anticoagulant treatment with warfarin or related drugs.

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it is caused by chronic, uncontrolled activation of the complement system, a branch of the body’s immune system that destroys and removes foreign particles. The disease affects both children and adults and is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to stroke, heart attack, kidney failure, and death. The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane cofactor protein), or is occasionally due to acquired neutralizing autoantibody inhibitors of these complement system components, for example anti–factor H antibodies. Despite the use of supportive care, historically an estimated 33–40% of patients died or developed end-stage renal disease (ESRD) with the first clinical bout of aHUS. Including subsequent relapses, a total of approximately two-thirds (65%) of patients died, required dialysis, or had permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI).

Thrombophilia (sometimes hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as deep vein thrombosis in the leg) that was not provoked by other causes. A significant proportion of the population has a detectable abnormality, but most of these only develop thrombosis in the presence of an additional risk factor.

There is no specific treatment for most thrombophilias, but recurrent episodes of thrombosis may be an indication for long-term preventative anticoagulation. The first major form of thrombophilia, antithrombin deficiency, was identified in 1965, while the most common abnormalities (including factor V Leiden) were described in the 1990s.

STEC-HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin(s), usually types of "E. coli", that expresses verotoxin (also called Shiga-like toxin). "E. coli" can produce stx1 and/or stx2 Shiga toxins, the latter being more dangerous and a combination of both toxins in certain ratios is usually associated with HUS. These Shiga toxins bind GB3 receptors, globotriaosylceramide, which are present in renal tissue more than any other tissue and are also found in central nervous system neurons and other tissue. Children have more GB3 receptors than adults which may be why children are more susceptible to HUS. Cattle, swine, deer, and other mammals do not have GB3 receptors, but can be asymptomatic carriers of Shiga toxin-producing bacteria. Some humans can also be asymptomatic carriers. Once the bacteria colonizes, diarrhea followed by bloody diarrhea, hemorrhagic colitis, typically follows. HUS develops about 5–10 days after onset of diarrhea, with decreased urine output (oliguria), blood in the urine (hematuria), kidney failure, thrombocytopenia (low levels of platelets) and destruction of red blood cells (microangiopathic hemolytic anemia). Hypertension is common. In some cases, there are prominent neurologic changes.

Patients with HUS commonly exhibit the signs and symptoms of thrombotic microangiopathy (TMA), which can include abdominal pain, low platelet count, elevated lactate dehydrogenase LDH, a chemical released from damaged cells, and which is therefore a marker of cellular damage) decreased haptoglobin (indicative of the breakdown of red blood cells) anemia (low red blood cell count)/schistocytes (damaged red blood cells), elevated creatinine (a protein waste product generated by muscle metabolism and eliminated renally, proteinuria (indicative of kidney injury), confusion, fatigue, edema (swelling), nausea/vomiting, and diarrhea. Additionally, patients with aHUS typically present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, and coma. Failure of neurologic, cardiac, renal, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression.

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

Thrombocytopenic purpura are purpura associated with a reduction in circulating blood platelets which can result from a variety of causes, such as kaposi sarcoma.

Individuals with congenital hypfibringenemia often lack any symptoms are detected by routine lab testing of fibrinogen or when tested for it because close relatives have symptomatic hypofibrinogenmeia. Indeed, studies indicate that, among family members with the identical congenital hypofibrinogenemia mutation, some never exhibit symptoms and those that are symptomatic develop symptoms only as adults.

Individuals with this disorder are usually less symptomatic than patients with other fibrinogen disorders because their fibrinogen levels are generally sufficient to prevent spontaneous bleeding. Those with particularly low blood fibrinogen levels (<0.5 gram/liter) may develop serious bleeding spontaneously and many with the disorder do so following trauma or surgery. Depending on their fibrinogen levels, women with the disorder may also bleed excessively during delivery and the postpartum period; in rare cases, they may have an increased risk of suffering miscarriages. Individuals with the disorder also suffer thrombotic events which may include blockage of large arteries in relatively young patients who have high levels of cardiovascular risk factors. The thrombi which form in these individuals are unstable, tend to embolize, and may therefore lead to thromboembolic events such as pulmonary embolism. Both bleeding and thrombotic events can occur at separate times or even concurrently in the same individual with the disorder.

Many cases of congenital dysfibrinogenemia are asymptomatic. Since manifestations of the disorder generally occur in early adulthood or middle-age, younger individuals with a gene mutation causing it may not have had time to develop symptoms while previously asymptomatic individuals of advanced age with such a mutation are unlikely to develop symptoms. Bleeding episodes in most cases of this disorder are mild and commonly involve easy bruising and menorrhagia. Less common manifestations of bleeding may be severe or even life-threatening; these include excessive bleeding after tooth extraction, surgery, vaginal birth, and miscarriage. Rarely, these individuals may suffer hemarthrosis or cerebral hemorrhage. In one study of 37 individuals >50 years old afflicted with this disorder, 19% had a history of thrombosis. Thrombotic complications occur in both arteries and veins and include transient ischemic attack, ischemic stroke, myocardial infarction, retinal artery thrombosis, peripheral artery thrombosis, and deep vein thrombosis. In one series of 33 individuals with a history of thrombosis due to congenital dysfibrinogenemia, five developed chronic pulmonary hypertension due to ongoing pulmonary embolism probably stemming form deep vein thrombosis. About 26% of individuals with the disorder suffer both bleeding and thrombosis complications.

The presentation of TTP is variable. The initial symptoms, which force the patient to medical care, are often the consequence of lower platelet counts like purpura (present in 90% of patients), ecchymosis and hematoma. Patients may also report signs and symptoms as a result of (microangiopathic) hemolytic anemia, such as (dark) beer-brown urine, (mild) jaundice, fatigue and pallor. Cerebral symptoms of various degree are present in many patients, including headache, paresis, speech disorder, visual problems, seizures and disturbance of consciousness up to coma. The symptoms can fluctuate so that they may only be temporarily present but may reappear again later in the TTP episode. Other unspecific symptoms are general malaise, abdominal, joint and muscle pain. Severe manifestations of heart or lung involvements are rare, although affections are not seldom measurable (such as ECG-changes).

Thrombotic Storm has been seen in individuals of all ages and races. The initial symptoms of TS present in a similar fashion to the symptoms experienced in deep vein thrombosis. Symptoms of a DVT may include pain, swelling and discoloration of the skin in the affected area. As with DVTs patients with TS may subsequently develop pulmonary emboli. Although the presentation of TS and DVTs are similar, TS typically progresses rapidly, with numerous clots occurring within a short period of time. After the formation of the initial clot a patient with TS typically begins a “clotting storm” with the development of multiple clots throughout the body. Rapid progression within a short period of time is often seen, affecting multiple organs systems. The location of the clot is often unusual or found in a spot in the body that is uncommon such as the dural sinus. Patients tend to respond very well to anticoagulation such as coumadin or low molecular weight heparin but may become symptomatic when treatment is withheld.

While the key clinical characteristics of thrombotic storm are still being investigated, it is believed that the clinical course is triggered by a preexisting condition, known as a hypercoagulable state. These can include such things as pregnancy, trauma or surgery. Hypercoagulable states can be an inherited or acquired risk factor that then serves as a trigger to initiate clot formation. However, in a subset of patient with TS a trigger cannot be identified. Typically people with TS will have no personal or family history of coagulations disorders.

Hemolytic-uremic syndrome (or haemolytic-uraemic syndrome), abbreviated HUS, is a disease characterized by a triad of hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia). It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of infectious, sometimes bloody, diarrhea acquired as a foodborne illness or from a contaminated water supply caused by , other non-O157:H7 "E. coli" serotypes, "Shigella", and "Campylobacter". A variety of viruses have also been implicated as a causative agent. It is now the most common cause of acquired acute renal failure in childhood. It is a medical emergency and carries a 5–10% mortality rate; of the remainder, the majority recover without major consequences, approximately 30% suffer residual renal injury. The primary target appears to be the vascular endothelial cell. This may explain the pathogenesis of HUS, in which a characteristic renal lesion is capillary microangiopathy.

HUS was first defined as a syndrome in 1955. The more common form of the disease, Shiga-like toxin-producing "E. coli" HUS (STEC-HUS), is triggered by the infectious agent "E. coli" O157:H7, and several other non-O157:H7 "E. coli" serotypes. Certain Shiga toxin-secreting strains of "Shigella dysenteriae" can also cause HUS. Approximately 5% of cases are classified as pneumococcal HUS, which results from infection by "Streptococcus pneumoniae", the agent that causes traditional lobar pneumonia. There is also a rare, chronic, and severe form known as atypical hemolytic uremic syndrome (aHUS), which is caused by genetic defects resulting in chronic, uncontrolled complement activation. Both STEC-HUS and aHUS cause endothelial damage, leukocyte activation, platelet activation, and widespread inflammation and multiple thromboses in the small blood vessels, a condition known as systemic thrombotic microangiopathy (TMA), which leads to thrombotic events as well as organ damage/failure and death.

The symptoms experienced in cholesterol embolism depend largely on the organ involved. Non-specific symptoms often described are fever, muscle ache and weight loss. Embolism to the legs causes a mottled appearance and purple discoloration of the toes, small infarcts and areas of gangrene due to tissue death that usually appear black, and areas of the skin that assume a marbled pattern known as "livedo reticularis". The pain is usually severe and requires opiates. If the ulcerated plaque is below the renal arteries the manifestations appear in both lower extremities. Very rarely the ulcerated plaque is below the aortic bifurcation and those cases the changes occur only in one lower extremity.

Kidney involvement leads to the symptoms of renal failure, which are non-specific but usually cause nausea, reduced appetite (anorexia), raised blood pressure (hypertension), and occasionally the various symptoms of electrolyte disturbance such as an irregular heartbeat. Some patients report hematuria (bloody urine) but this may only be detectable on microscopic examination of the urine. Increased amounts of protein in the urine may cause edema (swelling) of the skin (a combination of symptoms known as nephrotic syndrome).

If emboli have spread to the digestive tract, reduced appetite, nausea and vomiting may occur, as well as nonspecific abdominal pain, gastrointestinal hemorrhage (vomiting blood, or admixture of blood in the stool), and occasionally acute pancreatitis (inflammation of the pancreas).

Both the central nervous system (brain and spinal cord) and the peripheral nervous system may be involved. Emboli to the brain may cause stroke-like episodes, headache and episodes of loss of vision in one eye (known as amaurosis fugax). Emboli to the eye can be seen by ophthalmoscopy and are known as plaques of Hollenhorst. Emboli to the spinal cord may cause paraparesis (decreased power in the legs) or cauda equina syndrome, a group of symptoms due to loss of function of the distal part of the spinal cord - loss of control over the bladder, rectum and skin sensation around the anus. If the blood supply to a single nerve is interrupted by an embolus, the result is loss of function in the muscles supplied by that nerve; this phenomenon is called a "mononeuropathy".

Cryofibrinogenmic disease commonly begins in adults aged 40–50 years old with symptoms of the diseases occurring in the almost always affected organ, skin. Cutaneous symptoms include on or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Ranaud phenomena; cyanosis, s palpable purpura termed Cryofibrinogenemic purpura), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms. Patients also have a history of cold sensitivity (~25% of cases), arthralgia (14-58%), neuritis (7-19%), myalgia (0-14%); and overt thrombosis of arteries and veins (25-40%) which may on rare occasions involve major arteries such of those of the brain and kidney. Signs of renal involvement (proteinuria, hematuria, decreased glomerular filtration rate, and/or, rarely, renal failure) occur in 4-25% of cases. Compared to secondary cryofibrinogemia, primary crygofibrinogenemia has a higher incidence of cutaneous lesions, arthralgia, and cold sensitivity while having a far lower incidence of renal involvement. Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease. While rare, individuals with cryofibrinogemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates.

Thrombosis is generally defined by the type of blood vessel affected (arterial or venous thrombosis) and the precise location of the blood vessel or the organ supplied by it.

Deep vein thrombosis (DVT) is the formation of a blood clot within a deep vein. It most commonly affects leg veins, such as the femoral vein. Three factors are important in the formation of a blood clot within a deep vein—these are the rate of blood flow, the thickness of the blood and qualities of the vessel wall. Classical signs of DVT include swelling, pain and redness of the affected area.