Thrombocytopenia usually has no symptoms and is picked up on a routine full blood count (or complete blood count). Some individuals with thrombocytopenia may experience external bleeding such as nosebleeds, and/or bleeding gums. Some women may have heavier or longer periods or breakthrough bleeding. Bruising, particularly purpura in the forearms and petechiae in the feet, legs, and mucous membranes, may be caused by spontaneous bleeding under the skin.

Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. It is also important to ensure that the other blood cell types, such as red blood cells and white blood cells, are not also suppressed.

Painless, round and pinpoint (1 to 3 mm in diameter) petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue or yellow-green areas of skin that vary in size and shape. They can occur anywhere on the body.

A person with this disease may also complain of malaise, fatigue and general weakness (with or without accompanying blood loss). Acquired thrombocytopenia may be associated with a history of drug use. Inspection typically reveals evidence of bleeding (petechiae or ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Adults may have large, blood-filled bullae in the mouth. If the person's platelet count is between 30,000 and 50,000/mm, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/mm, spontaneous bruising will be seen (mostly on the arms and legs).

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.

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood.

A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000 per microliter.

High platelet levels do not necessarily signal any clinical problems, and are picked up on a routine full blood count. However, it is important that a full medical history be elicited to ensure that the increased platelet count is not due to a secondary process. Often, it occurs in tandem with an inflammatory disease, as the principal stimulants of platelet production (e.g. thrombopoietin) are elevated in these clinical states as part of the acute phase reaction.

High platelet counts can occur in patients with polycythemia vera (high red blood cell counts), and is an additional risk factor for complications.

A very small segment of patients report symptoms of erythromelalgia, a burning sensation and redness of the extremities that resolves with cooling and/or aspirin use.

Scientific literature sometimes excludes thrombocytosis from the scope of thrombophilia by definition, but practically, by the definition of thrombophilia as an increased predisposition to thrombosis, thrombocytosis (especially primary thrombocytosis) is a potential cause of thrombophilia. Conversely, secondary thrombocytosis very rarely causes thrombotic complications.

Immune thrombocytopenia (ITP) is a type of thrombocytopenic purpura defined as isolated low platelet count (thrombocytopenia) with normal bone marrow and the absence of other causes of thrombocytopenia. It causes a characteristic purpuric rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. The acute form often follows an infection and has a spontaneous resolution within two months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown.

ITP is an autoimmune disease with antibodies detectable against several platelet surface antigens.

ITP is diagnosed by a low platelet count in a complete blood count (a common blood test). However, since the diagnosis depends on the exclusion of other causes of a low platelet count, additional investigations (such as a bone marrow biopsy) may be necessary in some cases.

In mild cases, only careful observation may be required but very low counts or significant bleeding may prompt treatment with corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, or immunosuppressive drugs. "Refractory ITP" (not responsive to conventional treatment) may require splenectomy, the surgical removal of the spleen. Platelet transfusions may be used in severe bleeding together with a very low count. Sometimes the body may compensate by making abnormally large platelets.

Signs include the spontaneous formation of bruises (purpura) and petechiae (tiny bruises), especially on the extremities, bleeding from the nostrils and/or gums, and menorrhagia (excessive menstrual bleeding), any of which may occur if the platelet count is below 20,000 per μl. A very low count (<10,000 per μl) may result in the spontaneous formation of hematomas (blood masses) in the mouth or on other mucous membranes. Bleeding time from minor lacerations or abrasions is usually prolonged.

Serious and possibly fatal complications due to extremely low counts (<5,000 per μl) include subarachnoid or intracerebral hemorrhage (bleeding inside the skull or brain), lower gastrointestinal bleeding or other internal bleeding. An ITP patient with an extremely low count is vulnerable to internal bleeding caused by blunt abdominal trauma, as might be experienced in a motor vehicle crash. These complications are not likely when the platelet count is above 20,000 per μl.

Symptoms usually present from the period of birth to early childhood as: nose bleeds, bruising, and/or gum bleeding. Problems later in life may arise from anything that can cause internal bleeding such as: stomach ulcers, surgery, trauma, or menstruation. Abnormality of the abdomen, Epistaxis, Menorrhagia, Purpura, Thrombocytopenia, and prolonged bleeding time have also been listed as symptoms of various Giant Platelet Disorders.

Characteristically, there is increased mucosal bleeding:

- menorrhagia

- easy bruising

- epistaxis

- gingival bleeding

- gastrointestinal bleeding

- postpartum bleeding

- increased bleeding post-operatively.

The bleeding tendency is variable but may be severe. Hemarthrosis, particularly spontaneous, is very rare, in contrast to the hemophilias.

Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin, but impaired with other agonists such as ADP, thrombin, collagen or epinephrine.

Thrombocytosis (or thrombocythemia) is the presence of high platelet counts in the blood, and can be either primary (also termed essential and caused by a myeloproliferative disease) or reactive (also termed secondary). Although often symptomless (particularly when it is a secondary reaction), it can predispose to thrombosis in some patients. Thrombocytosis can be contrasted with thrombocytopenia, a loss of platelets in the blood.

In a healthy individual, a normal platelet count ranges from 150,000 and 450,000 per mm³ (or microlitre) (150–450 x 10/L). These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessary imply any form of disease. Nevertheless, counts over 750,000 (and especially over a million) are considered serious enough to warrant investigation and intervention.

Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skin or through an intravenous infusion, and a "low molecular weight" form that is generally given subcutaneously (administered under the skin). Commonly used low molecular weight heparins are enoxaparin, dalteparin, nadroparin and tinzaparin.

In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT will therefore not experience any symptoms. Typically the platelet count will fall 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day.

The most common symptom of HIT is enlargement or extension of a previously diagnosed blood clot, or the development of a new blood clot elsewhere in the body. This may take the form of clots either in arteries or veins, causing arterial or venous thrombosis, respectively. Examples of arterial thrombosis are stroke, myocardial infarction ("heart attack"), and acute leg ischemia. Venous thrombosis may occur in the leg or arm in the form of deep vein thrombosis (DVT) and in the lung in the form of a pulmonary embolism (PE); the latter usually originate in the leg but migrate to the lung.

In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever, chills, high blood pressure, a fast heart rate, shortness of breath, and chest pain. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots.

Giant platelet disorders can be further categorized:

- caused by auto-immune disorders, for example Immune thrombocytopenic purpura (ITP), and characterized by low platelet count, but high MPV (Mean-Platelet Volume).

- Caused by glycoprotein abnormalities: Bernard-Soulier syndrome, Velocardiofacial syndrome

- Caused by calpain defect: Montreal platelet syndrome

- Caused by alpha granules defect: Gray platelet syndrome

- Characterized by abnormal neutrophil inclusions: May-Hegglin anomaly, Sebastian syndrome

- With systemic manifestations: Hereditary macrothrombocytopenia with hearing loss, Epstein syndrome, Fechtner syndrome

- With no specific abnormalities: Mediterranean macrothrombocytopenia

- Harris platelet syndrome

Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.

Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis (the abnormal formation of blood clots inside a blood vessel) because platelets release microparticles that activate thrombin, thereby leading to thrombosis. When thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies that activate platelets. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood tests.

The treatment of HIT requires stopping heparin treatment, and both protection from thrombosis and choice of an agent that will not reduce the platelet count any further. Several alternatives are available for this purpose and mainly used are danaparoid, fondaparinux, argatroban and bivalirudin.

While heparin was discovered in the 1930s, HIT was not reported until the 1960s.

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.

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.

Most people with ET are without symptoms referable to ET at the time of diagnosis, which is usually ultimately made after noting an elevated platelet level on a routine complete blood count (CBC). The most common symptoms are bleeding (due to dysfunctional platelets), blood clots (e.g., deep vein thrombosis or pulmonary embolism), headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities; the most common signs are increased white blood cell count, reduced red blood cell count, and an enlarged spleen.

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".

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.

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).

The dysfibrinogenemias consist of three types of fibrinogen disorders in which a critical blood clotting factor, fibrinogen, circulates at normal levels but is dysfunctional. Congenital dysfibrinogenemia is an inherited disorder in which one of the parental genes produces an abnormal fibrinogen. This fibrinogen interferes with normal blood clotting and/or lyses of blood clots. The condition therefore may cause pathological bleeding and/or thrombosis. Acquired dysfibrinogenemia is a non-hereditary disorder in which fibrinogen is dysfunctional due to the presence of liver disease, autoimmune disease, a plasma cell dyscrasias, or certain cancers. It is associated primarily with pathological bleeding. Hereditary fibrinogen Aα-Chain amyloidosis is a sub-category of congenital dysfibrinogenemia in which the dysfunctional fibrinogen does not cause bleeding or thrombosis but rather gradually accumulates in, and disrupts the function of, the kidney.

Congenital dysfibrinogenmia is the commonest of these three disorders. Some 100 different genetic mutations occurring in more than 400 families have been found to cause it. All of these mutations as well as those causing hereditary fibrinogen Aα-Chain amyloidosis exhibit partial penetrance, i.e. only some family members with one of these mutant genes develop dysfibrinogenemia-related symptoms. While both of these congenital disorders as well as acquired dysfibrinogenemia are considered very rare, it is estimated that ~0.8% of individuals with venous thrombosis have either a congenital or acquired dysfibrinogenemia. Hence, the dysfibrinogenemia disorders may be highly under-diagnosed conditions due to isolated thrombotic events that are not appreciated as reflecting an underlying fibrinogen disorder.

Congenital dysfibrinogenemia is distinguished from a similar inherited disorder, congenital hypodysfibrinogenemia. Both disorders involve the circulation of dysfunctional fibrinogen but in congenital hypodysfibrinogenemia plasma fibrinogen levels are low while in congenital dysfibrinogenemia they are normal. Furthermore, the two disorders involve different gene mutations and inheritance patterns as well as somewhat different symptoms.

Frequently, the thrombocytopenia is mild and the affected neonates remain largely asymptomatic. In these cases, therapeutic interventions are not indicated. In case of severe thrombocytopenia, the neonates may exhibit hemorrhagic complication at or a few hours after delivery. The most serious complication is intracranial hemorrhage, leading to death in approximately 10% or neurologic sequelae in 20% of cases.

Post-transfusion purpura (PTP) is an adverse reaction to a blood transfusion or platelet transfusion that occurs when the body produces alloantibodies to the introduced platelets' antigens. These alloantibodies destroy the patient's platelets leading to thrombocytopenia, a rapid decline in platelet count. PTP usually presents 5–12 days after transfusion, and is a potentially fatal condition.

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.

The following revised diagnostic criteria for essential thrombocythaemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6. The criteria are as follows:

- A1. Platelet count > 450 × 10/µL for at least 2 months.

- A2. Acquired V617F JAK2 mutation present

- B1. No cause for a reactive thrombocytosis

- normal inflammatory indices

- B2. No evidence of iron deficiency

- stainable iron in the bone marrow or normal red cell mean corpuscular volume

- B3. No evidence of polycythemia vera

- hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores

- B4. No evidence of chronic myeloid leukemia

- But the Philadelphia chromosome may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially acute lymphocytic leukemia.

- B5. No evidence of myelofibrosis

- no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)

- B6. No evidence of a myelodysplastic syndrome

- no significant dysplasia

- no cytogenetic abnormalities suggestive of myelodysplasia

The clinical hallmark is haemorrhagic bullae on the mucosa of the oronasopharynx. Haemorrhage from ruptured bullae, epistaxis or gastrointestinal bleeding is severe and may cause shock and death.

Onyalai is an acute disease that results in the development of hemorrhagic lesions on oral, nasal, and subconjunctival mucous membranes and skin, including on the soles of the feet. The patient initially is not in distress, which may result in a delay of diagnosis. As the disease progresses, hematuria, melena and menorrhagia may develop. Bleeding usually persists for approximately eight days, and may recur. Approximately 80 percent of cases will develop chronic thrombocytopenia. Periodic episodes of acute hemorrhage are possible and may be severe, leading to shock and death.