Thrombocytopenia

Thrombocytopenia (or thrombopenia) is a relative decrease of platelets in 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 is a platelet count below 50,000 per microliter.

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 hemorrhages 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, 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 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
 * Wiskott–Aldrich 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
platelets deficiency-inducing medications include:
 * Direct myelosuppression
 * Valproic acid
 * Methotrexate
 * Carboplatin
 * Interferon
 * Isotretinoin
 * Panobinostat
 * Other chemotherapy drugs
 * Singulair (montelukast sodium)
 * H2 blockers and Proton-pump inhibitors have shown increased Thrombocytopenia symptoms, such as red dots near the bottom of the legs.

More extensive lists of thrombocytopenia-inducing medications are available.
 * 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.

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.

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, 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
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.

Neonatal thrombocytopenia
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

The interleukin-11 is being investigated as a potential drug for aiding thrombocytopenia management, especially in the cases of sepsis or necrotising enterocolitis (NEC).

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