From Wikipedia, the free encyclopedia
  (Redirected from Thrombocytopathy)
Jump to: navigation, search
Giant platelets.JPG
Image from a light microscope (40×) from a peripheral blood smear surrounded by red blood cells. One normal platelet can be seen in the upper left side of the image (purple) and is significantly smaller in size than the red blood cells (stained pink). Two giant platelets (stained purple) are also visible.
Latin thrombocytes
Code TH H2.
3D Rendering of Platelets

Platelets, or thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are small, disc shaped clear cell fragments (i.e., cells that do not have a nucleus), 2–3 µm in diameter,[1] which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days. Platelets are a natural source of growth factors. They circulate in the blood of mammals and are involved in hemostasis, leading to the formation of blood clots.




  • The physiological range for platelets is (150 – 400) × 103 per mm3 (also expressed as platelets per μL (microlitre) or ×109/L).
  • Megakaryocyte and platelet production is regulated by thrombopoietin, a hormone usually produced by the liver and kidneys.
  • Each megakaryocyte produces between 5,000 and 10,000 platelets.
  • Around 1011 platelets are produced each day by an average healthy adult.
  • Reserve platelets are stored in the spleen, and are released when needed by sympathetically induced splenic contraction.
  • The lifespan of circulating platelets is 5 to 9 days.

Thrombus formation[edit]


The function of platelets is the maintenance of hemostasis.  This is achieved primarily by the formation of thrombi, when damage to the endothelium of blood vessels occurs. Conversely, thrombus formation must be inhibited at times when there is no damage to the endothelium. These processes are regulated through thromboregulation.


The inner surface of blood vessels is lined with a thin layer of endothelial cells that, in normal hemostasis, acts to inhibit platelet activation by producing nitric oxide, endothelial-ADPase, and PGI2.  Endothelial-ADPase clears away the platelet activator, ADP.

Endothelial cells produce a protein called von Willebrand factor (vWF), a cell adhesion ligand, which helps endothelial cells adhere to collagen in the basement membrane. Under physiological conditions, collagen is not exposed to the bloodstream. vWF is secreted constitutively into the plasma by the endothelial cells, and is stored in granules within the endothelial cell and in platelets.

When the endothelial layer is injured, collagen, vWF and tissue factor from the subendothelium is exposed to the bloodstream. When the platelets contact collagen or vWF, they are activated (e.g. to clump together). They are also activated by thrombin (formed with the help of tissue factor). They can also be activated by a negatively charged surface, such as glass. Non-physiological flow conditions (especially high values of shear stress) caused by arterial stenosis or artificial devices (Mechanical Heart Valves, blood pumps etc.) can also lead to platelet activation.[10]

Platelet activation further results in the scramblase-mediated transport of negatively charged phospholipids to the platelet surface.  These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase and prothrombinase complexes. Calcium ions are essential for binding of these coagulation factors.

Shape change[edit]

Scanning electron micrograph of blood cells. From left to right: human erythrocyte, activated thrombocyte (platelet), leukocyte.


Granule secretion[edit]

Platelets contain alpha and dense granules.  Activated platelets excrete the contents of these granules into their canalicular systems and into surrounding blood.  There are three types of granules:

Thromboxane A2 synthesis[edit]

Platelet activation initiates the arachidonic acid pathway to produce TXA2.  TXA2 is involved in activating other platelets and its formation is inhibited by COX inhibitors, such as aspirin.

Adhesion and aggregation[edit]

Platelets clumping from a blood smear. May Grunwald-Giemsa. Light Microscopy, oil immersion 100x.

Platelets aggregate, or clump together, using fibrinogen and von Willebrand factor (vWF) as a connecting agent. The most abundant platelet aggregation receptor is glycoprotein IIb/IIIa (gpIIb/IIIa); this is a calcium-dependent receptor for fibrinogen, fibronectin, vitronectin, thrombospondin, and vWF. Other receptors include GPIb-V-IX complex (vWF) and GPVI (collagen).



Wound repair[edit]

The blood clot is only a temporary solution to stop bleeding; vessel repair is therefore needed. The aggregated platelets help this process by secreting chemicals that promote the invasion of fibroblasts from surrounding connective tissue into the wounded area to completely heal the wound or form a scar. The obstructing clot is slowly dissolved by the fibrinolytic enzyme, plasmin, and the platelets are cleared by phagocytosis.

ADP (purinergic/P2) receptors[edit]

Human platelets have three types of P2 receptors: P2X(1), P2Y(1) and P2Y(12). Although abnormalities in all three genes have been documented, but clinical correlation is available only for P2Y(12).[11] Patients with P2Y(12) defects have a mild to moderate bleeding diathesis, characterized by mucocutaneous bleeding and excessive post-surgical and post-traumatic blood loss. A defects in P2Y(12) should be suspected when ADP, even at concentrations ≥10 micro molar, is unable to induce full, irreversible platelet aggregation. Confirmation of the diagnosis is with tests that evaluate the degree of inhibition of adenylyl cyclase by ADP.

Other functions[edit]

Cytokine signaling[edit]

In addition to being the chief cellular effector of hemostasis, platelets are rapidly deployed to sites of injury or infection, and potentially modulate inflammatory processes by interacting with leukocytes and by secreting cytokines, chemokines, and other inflammatory mediators.[13][14][15][16] Platelets also secrete platelet-derived growth factor (PDGF).

Role in disease[edit]

Diagram of the internal structure of a platelet

High and low counts[edit]

A normal platelet count in a healthy individual is between 150,000 and 450,000 per μL (microlitre) of blood ((150–450)×109/L).[17]  Ninety-five percent of healthy people will have platelet counts in this range.  Some will have statistically abnormal platelet counts while having no demonstrable abnormality. However, if it is either very low or very high, the likelihood of an abnormality being present is higher.

Both thrombocytopenia and thrombocytosis may present with coagulation problems.  In general, low platelet counts increase bleeding risks; however there are exceptions (such as immune-mediated heparin-induced thrombocytopenia or paroxysmal nocturnal hemoglobinuria). High counts may lead to thrombosis, although this is mainly when the elevated count is due to myeloproliferative disorder.

Transfusion is generally used only to correct unusually low platelet counts (typically below (10–15)×109/L). Transfusion is contraindicated in thrombotic thrombocytopenic purpura (TTP), as it fuels the coagulopathy. In patients undergoing surgery, a level below 50×109/L is associated with abnormal surgical bleeding, and regional anaesthetic procedures such as epidurals are avoided for levels below 80×109/L.[18]

Normal platelet counts are not a guarantee of adequate function.  In some states, the platelets, while being adequate in number, are dysfunctional.  For instance, aspirin irreversibly disrupts platelet function by inhibiting cyclooxygenase-1 (COX1), and hence normal hemostasis.  The resulting platelets are unable to produce new cyclooxygenase because they have no DNA.  Normal platelet function will not return until the use of aspirin has ceased and enough of the affected platelets have been replaced by new ones, which can take over a week.  Ibuprofen, another NSAID, does not have such a long duration effect, with platelet function usually returning within 24 hours,[19] and taking ibuprofen before aspirin sometimes may prevent the irreversible effects of aspirin.[20]  Uremia, a consequence of renal failure, leads to platelet dysfunction that may be ameliorated by the administration of desmopressin.


Oral agents often used to alter/suppress platelet function include aspirin, clopidogrel, cilostazol, ticlopidine, ticagrelor and prasugrel.

Intravenous agents often used to alter/suppress platelet function include: abciximab, eptifibatide, tirofiban.

In addition to platelet transfusion, hematopoetic agents such as Oprelvekin, Romiplostim, and Eltrombopag can be used to increase platelet counts.


Disorders leading to a reduced platelet count:

Alloimmune disorders

Disorders leading to platelet dysfunction or reduced count:

Disorders featuring an elevated count:

Disorders of platelet adhesion or aggregation:

Disorders of platelet granule amount or release

Disorders of platelet metabolism

  • Decreased cyclooxygenase activity, induced or congenital
  • Storage pool defects, acquired or congenital

Disorders that compromise platelet signaling:

Disorders in which platelets play a key role:

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
Hemophilia Unaffected Prolonged Unaffected Unaffected
Aspirin Unaffected Unaffected Prolonged Unaffected
Thrombocytopenia Unaffected Unaffected Prolonged Decreased
Liver failure, early Prolonged Unaffected Unaffected Unaffected
Liver failure, end-stage 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 or unaffected
Factor XII deficiency Unaffected Prolonged Unaffected Unaffected
C1INH deficiency Unaffected Shortened Unaffected Unaffected


Although red blood cells had been known since van Leeuwenhoek (1632–1723), the German anatomist Max Schultze (1825–1874) was the first to describe platelets.[25][26]  He described "spherules" that were much smaller than red blood cells and that occasionally clumped and were found in collections of fibrous material


In transfusion medicine[edit]

Platelet concentrate.




Platelets do not need to be cross-matched to ensure immune compatibility between donor and recipient unless they contain a significant amount of red blood cells (RBCs). The presence of RBCs results in a reddish-orange color to the product, and is usually associated with whole-blood platelets. Apheresis methods are more efficient than “soft spin” centrifugation at isolating the specific components of blood needed. An effort is usually made to issue type specific platelets, but this is not as critical as it is with RBCs.


Platelets are stored under constant agitation at 20–24°C (68-75.2°F). Storage at room temperature provides an environment where any bacteria that are introduced to the blood component during the collection process may proliferate and subsequently cause bacteremia in the patient. Regulations are in place in the United States that require products to be tested for the presence of bacterial contamination before transfusion.[32]

Volume reduction of platelets[edit]



Thrombocytes of non-mammalian vertebrates differ from mammalian thrombocytes in having a nucleus and resembling B lymphocytes. These thrombocytes aggregate in response to thrombin, but not ADP, serotonin, nor adrenaline as in mammals.[35][36]

See also[edit]


  1. ^ Campbell, Neil A. (2008). Biology (8th ed.). London: Pearson Education. p. 912. ISBN 978-0-321-53616-7. "Platelets are pinched-off cytoplasmic fragments of specialized bone marrow cells. They are about 2–3µm in diameter and have no nuclei. Platelets serve both structural and molecular functions in blood clotting." 
  3. ^ O'Connell SM, Impeduglia T, Hessler K, Wang XJ, Carroll RJ, Dardik H (2008). "Autologous platelet-rich fibrin matrix as cell therapy in the healing of chronic lower-extremity ulcers". Wound Repair Regen 16 (6): 749–56. doi:10.1111/j.1524-475X.2008.00426.x. PMID 19128245. 
  4. ^ Sánchez M, Anitua E, Azofra J, Andía I, Padilla S, Mujika I (2007). "Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices". Am J Sports Med 35 (2): 245–51. doi:10.1177/0363546506294078. PMID 17099241. 
  5. ^ Knighton DR, Ciresi KF, Fiegel VD, Austin LL, Butler EL (1986). "Classification and treatment of chronic nonhealing wounds. Successful treatment with autologous platelet-derived wound healing factors (PDWHF)". Ann. Surg. 204 (3): 322–30. doi:10.1097/00000658-198609000-00011. PMC 1251286. PMID 3753059. 
  6. ^ Knighton DR, Ciresi K, Fiegel VD, Schumerth S, Butler E, Cerra F (1990). "Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula". Surg Gynecol Obstet 170 (1): 56–60. PMID 2403699. 
  7. ^ Celotti F, Colciago A, Negri-Cesi P, Pravettoni A, Zaninetti R, Sacchi MC (2006). "Effect of platelet-rich plasma on migration and proliferation of SaOS-2 osteoblasts: role of platelet-derived growth factor and transforming growth factor-beta". Wound Repair Regen 14 (2): 195–202. doi:10.1111/j.1743-6109.2006.00110.x. PMID 16630109. 
  8. ^ McAleer JP, Sharma S, Kaplan EM, Persich G (2006). "Use of autologous platelet concentrate in a nonhealing lower extremity wound". Adv Skin Wound Care 19 (7): 354–63. doi:10.1097/00129334-200609000-00010. PMID 16943701. 
  9. ^ Driver VR, Hanft J, Fylling CP, Beriou JM (2006). "A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers". Ostomy Wound Manage 52 (6): 68–70, 72, 74 passim. PMID 16799184. 
  10. ^ Kroll, M., J. Hellums, et al. (1996). "Platelets and shear stress." Blood 88(5) 1525-1541
  11. ^ Cattaneo M (2011) Molecular defects of the platelet P2 receptors.Purinergic Signal
  12. ^ Movat, HZ; Weiser, WJ; Glynn, MF; Mustard, JF (December 1965). "Platelet phagocytosis and aggregation.". The Journal of Cell Biology 27 (3): 531–43. doi:10.1083/jcb.27.3.531. PMID 4957257. 
  13. ^ Weyrich AS, Zimmerman GA (2004). "Platelets: signaling cells in the immune continuum". Trends Immunol. 25 (9): 489–95. doi:10.1016/ PMID 15324742. 
  14. ^ Wagner, DD; Burger, PC (December 2003). "Platelets in inflammation and thrombosis.". Arteriosclerosis, thrombosis, and vascular biology 23 (12): 2131–2137. doi:10.1161/01.ATV.0000095974.95122.EC. PMID 14500287. 
  15. ^ Diacovo, TG; Puri, KD; Warnock, RA; Springer, TA; von Andrian, UH (Jul 12, 1996). "Platelet-mediated lymphocyte delivery to high endothelial venules.". Science 273 (5272): 252–5. doi:10.1126/science.273.5272.252. PMID 8662511. 
  16. ^ Iannacone M. et al. (2005). "Platelets mediate cytotoxic T lymphocyte-induced liver damage". Nat Med 11 (11): 1167–9. doi:10.1038/nm1317. PMC 2908083. PMID 16258538. 
  17. ^ Parveen June Kumar, Michael L. Clark (2005). "8". Clinical Medicine (6th ed.). Elsevier Saunders. p. 469. ISBN 0-7020-2763-4. 
  18. ^ Van Veen, Joost J.; Nokes, Timothy J.; Makris, Mike (1 January 2010). "The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals". British Journal of Haematology 148 (1): 15–25. doi:10.1111/j.1365-2141.2009.07899.x. PMID 19775301. 
  19. ^ <Please add first missing authors to populate metadata.> (2005). "Platelet Function after Taking Ibuprofen for 1 Week". Annals of internal medicine 142 (7): I54. PMID 15809457. 
  20. ^ Rao, GH; Johnson, GG; Reddy, KR; White, JG (1983). "Ibuprofen protects platelet cyclooxygenase from irreversible inhibition by aspirin". Arteriosclerosis (Dallas, Tex.) 3 (4): 383–8. doi:10.1161/01.ATV.3.4.383. PMID 6411052. 
  21. ^ Erpenbeck L, Schön MP (2010). "Deadly allies: the fatal interplay between platelets and metastasizing cancer cells". Blood 115 (17): 3427–36. doi:10.1182/blood-2009-10-247296. PMC 2867258. PMID 20194899. 
  23. ^ Kornerup, KN; Page, CP (August 2007). "The role of platelets in the pathophysiology of asthma.". Platelets 18 (5): 319–28. doi:10.1080/09537100701230436. PMID 17654302. 
  24. ^ Laidlaw, TM; Kidder, MS; Bhattacharyya, N; Xing, W; Shen, S; Milne, GL; Castells, MC; Chhay, H; Boyce, JA (Apr 19, 2012). "Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes.". Blood 119 (16): 3790–8. doi:10.1182/blood-2011-10-384826. PMC 3335383. PMID 22262771. 
  28. ^ American Association of Blood Banks Standards for Blood Banks and Transfusion Services, Bethesda, MD: 22nd ed, AABB, 2003, Section
  29. ^ Hogman, C. F. (1992). "New trends in the preparation and storage of platelets". Transfusion 32 (1): 3–6. doi:10.1046/j.1537-2995.1992.32192116428.x. PMID 1731433. 
  30. ^ Ruane, Patrick H.; Edrich, Richard; Gampp, Deanna; Keil, Shawn D.; Leonard, R. Lynne; Goodrich, Raymond P. (1 June 2004). "Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light". Transfusion 44 (6): 877–885. doi:10.1111/j.1537-2995.2004.03355.x. PMID 15157255. 
  31. ^ Perez-Pujol, S. et al. (2005). "Effects of a New Pathogen-Reduction Technology (Mirasol PRT) on Functional Aspects of Platelet Concentrates". Transfusion 45 (6): 911–919. doi:10.1111/j.1537-2995.2005.04350.x. PMID 15934989. 
  32. ^ AABB Standards for Blood Banks and Transfusion Services 26th Edition Bethesda, MD: AABB, 2009.
  33. ^ Schoenfeld H, Spies C, Jakob C (2006). "Volume-reduced platelet concentrates". Curr. Hematol. Rep. 5 (1): 82–8. PMID 16537051. 
  35. ^ Blood v. 118 no. 13, 3661-3669 (29 September 2011); doi:10.1182/blood-2011-02-338244 Occlusive thrombi arise in mammals but not birds in response to arterial injury: evolutionary insight into human cardiovascular disease. Alec A. Schmaier, et al. [1]
  36. ^ Nature 220, 509 - 510 (2 November 1968); doi:10.1038/220509a0 ADP is not Involved in Thrombin-Induced Aggregation of Thrombocytes of a Non-mammalian Vertebrate FRANK A. BELAMARICH, DAVID SHEPRO & MARJA KIEN Biology Department, Boston University, Massachusetts.[2]

External links[edit]