A normal human platelet count ranges from 150,000 to 450,000 platelets per microlitre 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 is a platelet count below 50,000 per microlitre.
Signs and symptoms
Often, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine full blood count (or complete blood count). Occasionally, there may be bruising, particularly purpura in the forearms, petechia (pinpoint hemorrhages on skin and mucous membranes), nosebleeds, and/or bleeding gums.
Eliciting a full medical history is vital to ensure the low platelet count is not due to a secondary process. 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 bruises 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). In acquired thrombocytopenia, the patient's history may include the use of one or several offending drugs.
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/mm3, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/mm3, spontaneous bruising will be seen (mostly on the arms and legs).
Decreased platelet counts can be due to a number of disease processes:
- Vitamin B12 or folic acid deficiency
- Leukemia or myelodysplastic syndrome
- Decreased production of thrombopoietin by the liver in liver failure
- Sepsis, systemic viral or bacterial infection
- Dengue fever can cause thrombocytopenia by direct infection of bone marrow megakaryocytes, as well as immunological shortened platelet survival.
- Hereditary syndromes
- Congenital amegakaryocytic thrombocytopenia
- Thrombocytopenia absent radius syndrome
- Fanconi anemia
- Bernard-Soulier syndrome, associated with large platelets
- May-Hegglin anomaly, the combination of thrombocytopenia, pale-blue leuckocyte inclusions, and giant platelets
- Grey platelet syndrome
- Alport syndrome
- Wiskott–Aldrich syndrome
- Idiopathic 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
- Splenic sequestration of platelets due to hypersplenism
- Dengue fever has been shown to cause shortened platelet survival and immunological platelet destruction.
- HIV-associated thrombocytopenia
- Gaucher's disease
Thrombocytopenia-inducing medications include:
- Direct myelosuppression
- Immunological platelet destruction
- A drug molecule binds to the Fab portion of an antibody: A classic example is the quinidine group of drugs. The Fc portion of the antibody molecule is not involved in the binding process.
- A drug molecule binds to the Fc antibody moiety, with the drug/antibody complex subsequently binding and activating the platelets: Heparin-induced thrombocytopenia (HIT) is a classic example, in which the heparin-antibody-platelet factor 4 (PF4) complex binds to the Fc receptors on the surface of the platelet. Since the Fc moiety is now unavailable to the Fc receptors of the reticuloendothelial cells, the normally occurring destruction of the platelets is prevented. This may explain why severe thrombocytopenia is not a common feature of HIT.
- Abciximab-induced thrombocytopenia.
More extensive lists of thrombocytopenia-inducing medications are available.
- Snakebites, particularly by pit vipers.
- Onyalai, a disease of unknown etiology, is seen only in parts of Africa, but suspected of being caused by poor nutrition or consumption of tainted food.
- Excess consumption of oils containing erucic acid, such as Lorenzo's oil or mustard oil; see the side effects of taking Lorenzo's oil.
- Niacin Toxicity - Reversible thrombocyopenia has been observed in patients with niacin toxicity, particularly when large doses (3000mg/day) have been prescribed in patients with impaired renal function. The toxicity in this situation has been known to manifest itself in the form of increased renal impairment and declining platelet count.
Comparing coagulation tests
|Condition||Prothrombin time||Partial thromboplastin time||Bleeding time||Platelet count|
|Vitamin K deficiency or warfarin||Prolonged||Normal or mildly prolonged||Unaffected||Unaffected|
|Disseminated intravascular coagulation||Prolonged||Prolonged||Prolonged||Decreased|
|Von Willebrand disease||Unaffected||Prolonged or unaffected||Prolonged||Unaffected|
|Liver failure, early||Prolonged||Unaffected||Unaffected||Unaffected|
|Liver failure, end-stage||Prolonged||Prolonged||Prolonged||Decreased|
|Factor V deficiency||Prolonged||Prolonged||Unaffected||Unaffected|
|Factor X deficiency as seen in amyloid purpura||Prolonged||Prolonged||Unaffected||Unaffected|
|Bernard-Soulier syndrome||Unaffected||Unaffected||Prolonged||Decreased or unaffected|
|Factor XII deficiency||Unaffected||Prolonged||Unaffected||Unaffected|
If the cause for the low platelet count remains unclear, a bone marrow biopsy is usually recommended, to differentiate whether the low platelet count is due to decreased production or peripheral destruction.
Thrombocytopenia in hospitalized alcoholics may be caused by splenomegaly, folate deficiency, and, most frequently, a direct toxic effect of alcohol on production, survival time, and function of platelets. Platelet count begins to rise after 2 to 5 days' abstinence from alcohol. The condition is generally benign, and clinically significant hemorrhage is rare.
Lab tests to determine the platelet count and clotting function may also be done. In severe thrombocytopenia, a bone marrow study can determine the number, size and maturity of the megakaryocytes (the bone marrow cells that release mature platelets). This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time.
Treatment is guided by etiology and disease severity. The main concept in treating thrombocytopenia is to eliminate the underlying problem, whether that means discontinuing suspected drugs that cause thrombocytopenia, or treating underlying sepsis. Diagnosis and treatment of serious thrombocytopenia is usually directed by a hematologist.
Corticosteroids may be used to increase platelet production. Lithium carbonate or folate may also be used to stimulate the bone marrow production of platelets. Platelet transfusions may be used to stop episodic abnormal bleeding caused by a low platelet count. However, if platelet destruction results from an immune disorder, platelet infusions may have only a minimal effect and may be reserved for life-threatening bleeding.
Specific treatment plans often depend on the underlying etiology of the thrombocytopenia.
|Thrombotic thrombocytopenic purpura||Treatment of thrombotic thrombocytopenic purpura is a medical emergency, since the hemolytic anemia and platelet activation can lead to renal failure and changes in the level of consciousness. Treatment of TTP was revolutionized in the 1980s with the application of plasmapheresis. According to the Furlan-Tsai hypothesis, this treatment theoretically works by removing antibodies directed against the von Willebrand factor cleaving protease, ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease proteins to the patient, restoring a more physiological state of von Willebrand factor multimers. Patients with persistent antibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to explain the how plasmapheresis treats TTP.|
|Idiopathic thrombocytopenic purpura||Many cases of ITP can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts of under 50,000 are usually monitored with regular blood tests, and those with counts of under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with a platelet count this low. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s, and hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000—though there are documented exceptions to this observation.
Treatments for ITP include:
Thrombopoetin analogues have been tested extensively for the treatment of ITP. These agents had previously shown promise but had been found to stimulate antibodies against endogenous thrombopoietin or lead to thrombosis.
|Heparin-induced thrombocytopenia||Discontinuation of heparin is critical in a case of HITT. Beyond that, however, clinicians generally treat to avoid a thrombosis, and patients started directly on warfarin after a diagnosis of HITT are at excess risk of venous limb gangrene. For this reason, patients are usually treated with a type of blood thinner called a direct thrombin inhibitor such as lepirudin or argatroban, which are approved by the U.S. Food and Drug Administration (FDA). Other blood thinners sometimes used in this setting that are not FDA-approved for treatment of HITT include bivalirudin and fondaparinux. Platelet transfusions are not a routine component of the treatment of HITT, since thrombosis, not bleeding, is the usual associated problem in this illness.|
|Congenital amegakaryocytic thrombocytopenia||Bone Marrow/Stem Cell Transplant is the only thing that ultimately cures this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death until transplant is done, although this is not always the case.|
Thrombocytopenia affects a few percent of newborns, and its prevalence in neonatal intensive care units (NICU) is high. Normally, its course is mild and it resolves without consequences. Most of the cases of thrombocytopenia affect preterm birth infants and are results of placental insufficiency and/or fetal hypoxia. The other causes are less frequent, e.g. alloimmune, genetic, autoimmune, infection, DIC.
Thrombocytopenia that starts after the first 72 hours since birth is often the result of underlying sepsis or necrotising enterocolitis (NEC). In the case of infection the PCR tests may be useful for rapid pathogen identification and detection of antibiotic resistance genes. The possible pathogens may be fungus, bacteria and viruses, for example: Cytomegalovirus (CMV), Rubella virus, HIV, Staphylococcus sp., Enterococcus sp., Streptococcus agalactiae (GBS), Streptococcus viridans, Listeria monocytogenes, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Yersinia enterocolitica, Borrelia burgdorferi, Candida sp., Toxoplasma gondii. The severity of thrombocytopenia might be correlated with the type of a pathogen; some research indicates that the most severe cases are related to fungal or gram-negative bacterial infection. The pathogen may be transmitted during birth or prior to it, but also by breast feeding. or during transfusion
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