Thrombocytopenia

Thrombocytopenia
Classification and external resources
ICD-10	D69.6, P61.0
ICD-9	287.3, 287.4, 287.5
OMIM	188000 313900
DiseasesDB	27522
MedlinePlus	000586
MeSH	D013921

Thrombocytopenia (or -paenia, or thrombopenia in short ) is the presence of relatively few platelets in blood.

Generally speaking, in human beings a normal 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 is a platelet count below 50,000 per microliter. The number of platelets in a blood sample also decreases rather quickly with time and a low platelet count may be caused by a delay between sampling and analysis.

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 CBC, complete blood count). Occasionally, there may be bruising, particularly purpura in the forearms,petechia (pinpoint hemmorages on skin and mucous membranes) nosebleeds and/or bleeding gums.

It is vital that a full medical history is elicited, 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 red blood cells, and white blood cells, are not also suppressed. Painless, round and pinpoints (1 to 3 mm in diameter), petechiae usually appear and fade, and sometimes group to form ecchymoses. Another type of blood leakage (and larger than petechiae), ecchymoses are purple, blue or yellow-green bruises that vary in size and shape. They can occur anywhere on the body from a traumatic injury.

A person with thrombocytopenia 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).

Causes

Decreased platelet counts can be due to a number of disease processes:

Decreased production

• 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 (CAMT)
  • 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

Increased destruction

• Idiopathic thrombocytopenic purpura (ITP)
• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic-uremic syndrome (HUS)
• Disseminated intravascular coagulation (DIC)
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Antiphospholipid syndrome
• Systemic lupus erythematosus (SLE)
• Post-transfusion purpura
• Neonatal alloimmune thrombocytopenia (NAITP)
• Splenic sequestration of platelets due to hypersplenism
• Dengue fever has been shown to cause shortened platelet survival and immunological platelet destruction
• HIV-associated thrombocytopenia

Medication-induced

Thrombocytopenia-inducing medications include:

• Direct myelosuppression
  • Valproic acid
  • Methotrexate
  • Carboplatin
  • Interferon
  • Isotretinoin
  • Other chemotherapy drugs
  • H2 blockers and Proton-pump inhibitors have shown increased Thrombocytopenia symptoms, such as red dots near the bottom of the legs.
• Immunological platelet destruction
  • Drug binds Fab portion of an antibody. The classic example of this mechanism is the quinidine group of drugs. The Fc portion of the antibody molecule is not involved in the binding process.
  • Drug binds to Fc, and drug-antibody complex binds and activates platelets. Heparin induced thrombocytopenia (HIT) is the classic example of this phenomenon. In HIT, the heparin-antibody-platelet factor 4 (PF4) complex binds to Fc receptors on the surface of the platelet. Since Fc portion of the antibody is bound to the platelets, they are not available to the Fc receptors of the reticulo-endothelial cells, so therefore this system cannot destroy platelets as usual. 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.

Other causes

• Snakebites, particularly by pit vipers.
• Onyalai, a disease of unknown etiology seen only in parts of Africa, but suspected of being caused by poor nutrition or consumption of tainted food.

Comparing coagulation tests

Condition	Prothrombin time	Partial thromboplastin time	Bleeding time	Platelet count
Vitamin K deficiency or Warfarin	prolonged	prolonged	unaffected	unaffected
Disseminated intravascular coagulation	prolonged	prolonged	prolonged	decreased
Von Willebrand disease	unaffected	prolonged	prolonged	unaffected
Haemophilia	unaffected	prolonged	unaffected	unaffected
Aspirin	unaffected	unaffected	prolonged	unaffected
Thrombocytopenia	unaffected	unaffected	prolonged	decreased
Early Liver failure	prolonged	unaffected	unaffected	unaffected
End-stage Liver failure	prolonged	prolonged	prolonged	decreased
Uremia	unaffected	unaffected	prolonged	unaffected
Congenital afibrinogenemia	prolonged	prolonged	prolonged	unaffected
Factor V deficiency	prolonged	prolonged	unaffected	unaffected
Factor X deficiency as seen in amyloid purpura	prolonged	prolonged	unaffected	unaffected
Glanzmann's thrombasthenia	unaffected	unaffected	prolonged	unaffected
Bernard-Soulier syndrome	unaffected	unaffected	prolonged	decreased

Diagnosis

Laboratory tests might include: full blood count, liver enzymes, renal function, vitamin B₁₂ levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear.

If the cause for the low platelet count remains unclear, bone marrow biopsy is often undertaken, 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

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.

Condition	Treatment
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: Prednisone and other corticosteroids Intravenous immune globulin Splenectomy Danazol Eltrombopag Rituximab Romiplostim 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. Romiplostim (trade name Nplate, formerly AMG 531) was found to be safe and effective for the treatment of ITP in refractory patients, especially those who relapsed following splenectomy.
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.

Veterinary treatment

Thrombocytopenia caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections is treated with Lymphocyte T-Cell Immune Modulator.

External links

• Thrombocytopenia types, causes, symptoms, and other details
• 11-133b. at Merck Manual of Diagnosis and Therapy Professional Edition
• Thrombocytopenia Forum
• Flourouracil/5-FU Toxicity & DPD Deficiency Education - DPD-Deficiency.com

cs:Trombocytopenie tr:Trombositopeni