Thrombocytopenia

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Thrombocytopeni
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 humans, a normal platelet count ranges from 150,000 and 450,000 per mm³.^[1] These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply any form of disease. 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.

One common definition is a number less than 100,000.^[2][3]

Contents 1 Signs and symptoms 2 Diagnosis 3 Causes 3.1 Decreased production 3.2 Increased destruction 3.3 Medication-induced 4 Treatment 5 Veterinary treatment 6 References 7 External links

[edit] 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, 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.

[edit] 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.

[edit] Causes

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

[edit] 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

[edit] 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^[4]

[edit] Medication-induced

Thrombocytopenia-inducing medications include:

• Direct myelosuppression
  • Valproic acid
  • Methotrexate
  • Carboplatin
  • Interferon
  • Other chemotherapy drugs
  • H2 Blockers and Proton Pump Inhibitors have shown increased Thrombocytopenia symptoms, such as red dots near the bottom of the legs^[5].
• 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.

More extensive lists of thrombocytopenia-inducing medications are available.^[6]

[edit] 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.

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[7][8], 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 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 thrombopoeitin 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.[9][10][11]
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.

[edit] Veterinary treatment

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

[edit] References

[edit] 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

v • d • e Pathology: hematology · myeloid hematologic disease (primarily D50-D77 · 280-289) Red blood cells ↑ Polycythemia · Macrocytosis ↓ Anemia Nutritional Micro-: Iron deficiency anemia (Plummer-Vinson syndrome) Macro-: Megaloblastic anemia (Pernicious anemia) Hemolytic (mostly Normo-; thalassemia) Hereditary enzymopathy: G6PD · glycolysis (PK, TI, HK) hemoglobinopathy: Thalassemia (alpha, beta, delta)  · Sickle-cell disease/trait · HPFH membrane: Hereditary spherocytosis (Minkowski-Chauffard syndrome) · Hereditary elliptocytosis (Ovalocytosis) · Hereditary stomatocytosis Acquired Autoimmune (WAHA, CAD, PCH) membrane (PNH) MAHA · TM (HUS) Drug-induced autoimmune hemolytic anemia · Drug-induced nonautoimmune hemolytic anemia Aplastic (mostly Normo-) Hereditary: Fanconi anemia · Diamond-Blackfan anemia Acquired: PRCA · Sideroblastic anemia · Myelophthisic Blood tests MCV (Normocytic, Microcytic, Macrocytic) · MCHC (Normochromic, Hypochromic) Other Methemoglobinemia · Sulfhemoglobinemia · Reticulocytopenia Coagulation/ coagulopathy/ bleeding diathesis ↑ Thrombocytosis Essential thrombocytosis Hypercoagulability primary: Antithrombin III deficiency · Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden · Hyperprothrombinemia acquired: DIC (Congenital afibrinogenemia, Purpura fulminans) · autoimmune (Antiphospholipid) ↓ Thrombocytopenia/ purpura Nonthrombocytopenic purpura: Henoch-Schönlein Thrombocytopenic purpura: ITP (Evans syndrome) · TM (TTP) Heparin-induced thrombocytopenia Platelet function adhesion (Bernard-Soulier syndrome) · aggregation (Glanzmann's thrombasthenia) · platelet storage pool deficiency (Hermansky-Pudlak syndrome, Gray platelet syndrome) Clotting factor Hemophilia (A/VIII, B/IX, C/XI) • Von Willebrand disease • Hypoprothrombinemia/II · XIII Monocytes/ macrophages ↑ Histiocytosis · Chronic granulomatous disease -cytosis: Monocytosis ↓ -penia: Monocytopenia Granulocytes ↑ -cytosis: granulocytosis (Neutrophilia, Eosinophilia, Basophilia, Bandemia) ↓ -penia: Granulocytopenia/agranulocytosis (Neutropenia/Kostmann syndrome · Eosinopenia · Basopenia) see also myeloid malignancy and immune disorders ↑ means increased, ↓ means decreased