PPPlatelets are derived from marrow megakaryocytes. Each mature megakaryocyte gives rise 1 000 to 8000 wafers.Platelets are cytoplasmic fragments mature megakaryocyte, and therefore are anucleate cells, incapable of synthesis.The lifetime of platelets is about 9 days. Normal platelet count in humans is 150-400109 / L and thrombocytopenia is defined as a platelet count less than 150,109 / L. Blood platelets play a central role in the mechanisms of primary haemostasis. Primary hemostasis is the set of complex interactions between platelets, vascular wall, and the adhesive proteins that result in the closure of vascular breach by a white platelet thrombus. Blood platelets are also involved in coagulation, which will allow the formation of fibrin from consolidating platelet aggregates. Blood platelets are involved in stopping bleeding, and hemorrhagic clinical manifestations may reflect severe thrombocytopenia. Using count controllers making routine platelet count, results in the discovery subclinical thrombocytopenia.
The Hemorrhagic syndrome to abnormal primary hemostasis [thrombocytopenia and (or) thrombopathy] is mucocutaneous. It is characterized by the occurrence of spontaneous purpura, if not erasing the pressure with petechiae (purple dots), bruises (violet blue cupboards), the vibices (elongated streaks Ecchymotic) of gingival bleeding, epistaxis, of oral ecchymotic bubbles. Menorrhagia or gastrointestinal bleeding is a feature of hemorrhagic syndrome. The severity of bleeding events is dominated by the cerebral subarachnoid hemorrhage, medical emergency with life threatening. It is preceded by bleeding in the fundus, which in severe thrombocytopenia examination of the fundus. It is therefore essential to assess the seriousness of the hemorrhagic syndrome. An extensive purpura, mouth Ecchymotic bubbles and retinal hemorrhages are serious factors prior intracranial hemorrhage. Hemorrhagic manifestations may occur when the platelet count is less than 100 109 / L if they are favored by underlying cause, while they are the sole fact of thrombocytopenia for lower platelet 50.109 / L and above 20.109 / L. Field (age, vascular risk factors, central thrombocytopenia) may aggravate the risk of bleeding. Clinical examination is essential for the etiological thrombocytopenia. The interrogation made clear personal and family history of hemorrhagic syndrome, thrombocytopenia notion. This examination must be “policeman” on the research drug intake before few days the onset of thrombocytopenia. Seeking hepatomegaly, of signs of portal hypertension, splenomegaly, tumor syndrome, a recent viral infection, recurrent infections, circumstances of onset (sudden isolated thrombocytopenia), the notion known affection, being the treatments, and context (fever, general condition) are the etiological factors.
Differential diagnosis :
Thrombocytopenia must always be checked by a finger stick or sodium citrate, since there are false thrombocytopenia by agglutination of platelets in vitro in the presence of anticoagulant EDTA (ethylene diamine tetra-acetic acid) on which the blood is collected. The existence of in vitro platelet aggregates can be checked on the stained blood smears.There are some cases of platelet agglutination EDTA independent, linked to antibodies directed against epitopes of the GP IIb-IIIa complex, which are exposed after dissociation of the GP IIb-IIIa complex by the chelating effect of calcium EDTA. These false thrombocytopenia are artifacts in vitro.
Orientation of the etiologic diagnosis:
If the clinical examination is crucial, blood count provides important information for the diagnosis, showing the isolated or non thrombocytopenia, appearance of blade plates (large or small pads in some constitutional thrombocytopenia, appearance gray chips feature of gray platelet disease). Thrombocytopenia can be associated with abnormalities of other lineages (leukemic process) or be part of an overall pancytopenia (aplastic anemia). Thrombocytopenia can be associated with hypochromic microcytic anemia in case of significant bleeding disorder, or macrocytic anemia (folate deficiency, vitamin B12, myelodysplasia). Simple tests of hemostasis seek liver failure or consumer signs [activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen assay]. Liver function tests may help in the diagnosis of liver damage responsible for thrombocytopenia before clinical signs. Depending on the clinical history, data count and hemostasis, bone marrow aspiration will be realized or not (Table I). The bone marrow aspiration distinguishes central thrombocytopenia with platelet disorder production of peripheral thrombocytopenia with platelet hyperdestruction.
Differential diagnosis:
A- thrombocytopenia devices:
They are secondary to platelet hyperdestruction or a distribution anomaly. The myelogram is normal with a wealth of megakaryocytes normal or increased. It is not routinely performed. The lifetime of platelets is shortened, but have not been investigated in case of difficulty in diagnosis (Table I).
1- platelet Hyperdestruction:
It is of immunological origin or consumption, and in this case the thrombocytopenia is associated with other abnormalities of hemostasis.
• immunological destruction of platelets – Autoimmune thrombocytopenic purpura It is due to the production of antiplatelet autoantibodies which bind by their F (ab) on platelets. Platelets are then destroyed by the system of macrophages which possess a receptor for the Fc fragment of immunoglobulins. The spleen is the privileged place of platelet destruction by macrophages and is also the key seat of the production of antiplatelet antibodies. The antibodies of the immune thrombocytopenic purpura are specific glycoproteins of the platelet membrane GP IIb-IIIa and GP Ib-IX. The immune thrombocytopenic purpura is a common condition, in good standing in young patients but affecting all age groups and especially children less than 10 years. We must differentiate autoimmune thrombocytopenic purpura in children that often occurs after a viral infection (including thrombocytopenia, which can be deep, will correct itself spontaneously in 80% of cases), the immune thrombocytopenic purpura of adult who becomes chronic in 80% of cases.
Hemorrhagic syndrome is not always correlated with the severity of thrombocytopenia, but platelet numbers below 20,109 / L require emergency treatment. The severity of the hemorrhagic syndrome is dominated by the cerebral subarachnoid hemorrhage may be responsible for death in 3% of cases. Thrombocytopenia is brutal, isolated. Myelogram when performed shows normal marrow, rich in megakaryocytes. Hemostasis is normal (activated partial thromboplastin time, prothrombin time) without evidence of consumption. The search for antiplatelet antibodies IgG or IgM rule is performed by ELISA. It is positive in 85% of cases. The specificity of these autoantibodies is carried out by the MAIPA method (Monoclonal antibody specific immobilization of platelet antigens), and they are directed against the rule of platelet membrane glycoprotein (GP IIb-IIIa, Ib-IX). If the kinetics were achieved, platelet life span would be less than 12-24 hours. The treatment of the acute phase to less than or equal to 20,109 platelets / L based on corticosteroids. A loading dose in the form of intravenous methylprednisolone (15 mg / kg / day x 3 days) may be performed, followed by oral prednisone 1 mg / kg / day for 15 days with progressive decrease. Treatment with intravenous immunoglobulin (0.4 g / kg / day x 3 days) is justified in severe hemorrhagic syndrome relay with oral prednisone. Platelet transfusions are against-indicated, unless immediate vital risk. Splenectomy is for forms of chronic thrombocytopenic purpura autoimmune after failure of conventional treatments. She was not carried out after 6 months of evolution after vaccination against pneumococcus and Haemophilus. Splenectomy leads to correction of immune thrombocytopenic purpura in 80% of cases. In refractory forms of autoimmune thrombocytopenic purpura after splenectomy, dapsone (dapsone), danazol (Danatrol), the vinca alkaloids (vincristine), cyclophosphamide (Cytoxan) have been proposed. Before a relapse of autoimmune thrombocytopenic purpura, spleen accessory search should be performed.
– Special forms of immune thrombocytopenic purpura: in a mother with immune thrombocytopenic purpura, thrombotic whether or not the newborn may have a neonatal thrombocytopenia linked to the passage of maternal autoantibodies;thrombocytopenic purpura autoimmune can be observed in the primary antiphospholipid syndrome and lupus.Thrombocytopenia is then associated with other autoimmune manifestations clinical and laboratory. The syndrome primary antiphospholipid is characterized by venous thrombosis and (or) artery, spontaneous abortions, the presence of lupus anticoagulant and (or) to anticardiolipid. Autoimmune thrombocytopenia, moderate rule, can be part of this picture. antiphospholipid syndrome can be part of lupus. The existence of anti-DNA antibodies, decreased further in favor of this diagnosis; thrombocytopenic purpura autoimmune may be associated with hematological malignancies (Hodgkin or non-Hodgkin’s lymphoma), viral diseases (cytomegalovirus, hepatitis B and C, human immunodeficiency virus). Autoimmune thrombocytopenia may be the first manifestation of the serology of the human immunodeficiency virus.
– Drug thrombocytopenia Their mechanism is complex. Fixing medicament immune complex and (or) anti-drug antibody metabolite or the fixing of the drug on platelets, may modify the membrane structure and make neo-antigens responsible for the synthesis of antiplatelet antibodies. The secondary immuno-allergic thrombocytopenia with the absorption of a drug is observed after several days of treatment (6-15 days). It is isolated, with no abnormalities of hemostasis, the accident is brutal, unrelated to the dose administered, and involves stopping the medication.Thrombocytopenia was reversible in about ten days after stopping the drug. Many drugs may be responsible for drug-induced thrombocytopenia, and those who are most often involved are: quinine, quinidine, sulfa drugs, digoxin, anti-inflammatory drugs, hydantoin, gold salts; it is the same for heroin and cocaine. The search for antiplatelet antibody in the presence of the offending drug may be useful in diagnosis. Among these drugs, it should be noted heparin that causes severe thrombocytopenia, accompanying himself of arterial thrombotic complications and (or) vein, which is unique for thrombocytopenia immuno allergic drug. Laboratory diagnosis, sometimes difficult, based on tests of platelet aggregation in patient serum and the presence of the administered heparin. There are many false negatives.The mechanism is related to the interaction of an antibody (IgG) recognizing the heparin-platelet factor IV complex and causing platelet activation by its binding to Fc g platelet II receptor. The immuno-allergic thrombocytopenia with heparin involve the need to monitor platelet count 2 times a week for a heparin treatment for 2 months and involve the discontinuation of heparin if they occur. The kinetics of appearance of thrombocytopenia compared to drug intake is important for diagnosis of drug-induced thrombocytopenia between the 6th and 15th day, except in cases of prior use.The examination must be thorough. Treatment consists of drug discontinuation. Platelet transfusions are deleterious and worse. If thrombocytopenia to heparin, with thrombotic complications or need for further antithrombotic therapy, treatment with recombinant hirudin (Refludan) or danaparoid (Orgaran) have been proposed.
– Post-transfusion thrombocytopenia are rare, isolated, severe and occur 7-10 days after transfusion of red cells in women. They are linked to an allo-antibody against a platelet antigen with sensitization during pregnancy or previous transfusions. The antibody is directed against HPA-Ia antigen (PLA1); HPA-Ib (PLA2), HPA-3 (Bak), HPA-4 (Pen). The allo-antigens are located on GPIIb or GPIIIa. The scarcity of thrombocytopenia is related to the low frequency of HPA-Ia negative population (2%) and individual susceptibility (HLA-DR3 topic).
• Platelet Consumption
– Disseminated intravascular coagulation (DIC) The clinical setting is evocative: infections, surgical setting, malignancy, obstetric complications, extend trauma, burns, intravascular hemolysis. Hemorrhagic syndrome can be important, and it is particularly with hemorrhage sheet and extensive bruising. Thrombocytopenia is variable severity, and is associated with consumption of other coagulation factors: factor V, factors VII, X, II and fibrinogen. The presence of soluble complexes (fibrin monomers) and D-dimer (fibrin degradation products) confirms the disseminated intravascular coagulation. The mechanism of coagulation is related to activation thereof generated by tissue factor overexpression. The generation of tissue factor in the presence of Factor VII results in the activation of coagulation and thrombin generation. Thrombin thus formed in excess, active coagulation phenomenon of positive feedback. The microthrombus training in traffic leads to organ failure, and within these microthrombus, there is a consumption of platelets and clotting factors. Treatment consists of treating the cause and heparin (low molecular weight heparin). In cases of severe thrombocytopenia less than 20 109 / L, platelet transfusions may be necessary if the hemorrhagic syndrome is threatening.
– Thrombotic Thrombocytopenic Purpura (Moschcowitz syndrome) and hemolytic uremic syndrome child thrombotic microangiopathy This combines clinically neurological signs (headache, paresis, aphasia, dysarthria), fever and renal disease (hypertension, edema the lower limbs). Thrombocytopenia is secondary to consumption. It is associated with a mechanical haemolytic anemia schistocytes by fragmentation of red blood cells in contact microthrombi in the microcirculation. Serum electrolytes control kidney function. – Kasabach-Merritt syndrome Some extensive angiomas are associated with platelet consumption by thrombocytopenia at angiomas. Thrombocytopenia is isolated and (or) associated with the presence of soluble complex and the increase of D-dimer.
– Extracorporeal circuits All extracorporeal circuit may be responsible for thrombocytopenia with platelet consumption at the foreign prosthetic circuit. Thrombocytopenia is associated with a secondary platelet disorder in platelet activation on foreign equipment.
2- distribution of Anomalies:
Thrombocytopenia dilution are observed in cases of massive red cell transfusions. It is the same for pregnancy where moderate thrombocytopenia dilution is observed during the last quarter. Any splenomegaly whatever the cause may be responsible for an increased sequestration of platelets. In a normal spleen, 30% of the platelet mass is sequestered, and this sequestration can reach 50 to 90% of the total platelet mass in case of splenomegaly.
3- Special case:
• Platelet Syndrome pseudo-Willebrand: very rare, autosomal dominant, this syndrome is characterized by a prolonged bleeding time, moderate thrombocytopenia with large platelets associated with decreased von Willebrand factor. There is a malfunction of the GP Ib responsible for excessive fastening von Willebrand factor which causes abnormal platelet aggregation and consumption of von Willebrand factor on the platelet membrane. Thrombocytopenia is isolated or associated with iron deficiency anemia related to bleeding. The plasma level of von Willebrand factor is decreased.
B- thrombocytopenia plants:
They are detailed in Table II.
1- Constitutional:
Exceptional, they affect only the megakaryocytic lineage or show an overall myelosuppression as Fanconi anemia.Some are associated with a thrombopathy.
• congenital amegakaryocytic with radial aplasia: Severe thrombocytopenia is associated with multiple skeletal malformations, heart, kidneys. Myelogram not found megakaryocytes. The other lines are normal.
• Congenital thrombocytopenia with autosomal dominant: thrombocytopenia varies in severity with large platelets. The life span of platelets is normal, the myelogram shows megakaryocytes normal in number but there is an abnormality of the release of platelets in the bone marrow.
• congenital aplastic anemia (Fanconi anemia) disease autosomal recessive transmission, it combines a malformation syndrome, psychomotor retardation, and bone marrow depression develops gradually in 4-10 years. Thrombocytopenia is the constant initial element, isolated or associated with a non-regenerative anemia and neutropenia. The evolution is characterized by the move towards myelosuppression with its complications and a high incidence of leukemia. The karyotype abnormalities found in type fracture and chromosomal rearrangements reflecting chromosomal fragility.
• Thrombocytopenia with thrombopathies
– Jean-Bernard Soulier disease and thrombotic or dystrophy hémorragipare This disease transmission autosomal recessive combines a major increase in bleeding time (BT), thrombocytopenia with large platelets, abnormal platelet adhesion to von factor Willebrand subendothelial default platelet glycoprotein complex Ib-IX. The study of platelet aggregation highlights an absence of agglutination in the presence of ristocetin while the other inductors (adenosine diphosphate, collagen) induce a normal aggregation.
– Illness gray platelet It combines a prolonged bleeding time, moderate thrombocytopenia with large platelets and gray after staining the blade inserts. It is characterized by an absence of intraplatelet alpha granules. It is autosomal dominant. Myelofibrosis is constant in this thrombopathy by secretion of PDGF (platelet-derived growth factor), for lack of storage in platelet alpha granules.
– Illness May-Hegglin Transmitted on autosomal dominant fashion, it combines thrombocytopenia with giant platelets and the presence of Dohle bodies in granulocytes. Hemorrhagic syndrome remains moderate. Thrombocytopenia is isolated.
– Wiskott-Aldrich Àtransmission sex-linked thrombocytopenia is severe with platelet microcytosis and abnormal T cells responsible eczema, recurrent infections. There is a dysmégacaryocytopoïèse with normal quantitatively but qualitatively abnormal megakaryocytes, abnormal platelet production managers with shortened platelet lifetime.
2- Acquired:
The stations acquired thrombocytopenia related to aplastic anemia or bone marrow infiltration. In these central thrombocytopenia, thrombocytopenia may not be isolated. It may be associated with pancytopenia (aplasia) or abnormal cell proliferation. The bone marrow aspiration and (or) bone marrow biopsy found an absence or hypoplasia megakaryocytic isolated or associated with bone marrow failure-hypoplasia more global or objectify bone marrow infiltration by tumor proliferation. Life measuring platelets is not indicated and it would be normal (8-10 days).
• acquired amegakaryocytic isolated: it can be of immunological origin, affecting only the megakaryocytic lineage, responsible for isolated severe thrombocytopenia. A particular form of cyclic amegakaryocytic in women may precede a persistent thrombocytopenia. It can be toxic, such as acute alcohol intoxication blocking megakaryopoiesis the stage of mature megakaryocytes and causes thrombocytopenia.
• Aplastic anemia acquired: thrombocytopenia pancytopenia is one of the elements that combines aplastic anemia, neutropenia. The diagnosis is confirmed by bone marrow aspiration and bone marrow biopsy showing the hypoplastic or aplastic anemia with no precursors affecting 3 lines. Different etiologies must be sought:
– The idiopathic aplastic are in order of immunological origin. Thrombocytopenia is associated with aplastic anemia and neutropenia. The bone marrow aspiration and bone marrow biopsy found a very poor marrow or desert; – Myelosuppression may be secondary to chemotherapy, radiation. Thrombocytopenia within the scope of aplasia and is transient;
– Medicated toxic (chloramphenicol, gold salts, sulfonamides, anti-inflammatory drugs, neuroleptics) or chemical (benzene) may be responsible for severe aplastic anemia with thrombocytopenia is one of the elements;
– Deep deficiencies of vitamin B12 and (or) folate are responsible for thrombocytopenia which is associated with a non-regenerative macrocytic anemia and neutropenia with polymorphonuclear Hypersegmented. Myelogram found signs of dysmyelopoiesis with megaloblastosis. The vitamin treatment allows recovery hematological abnormalities with a reticulocyte crisis in the 8th to 10th day;
– In the myelodysplasia, thrombocytopenia may precede the macrocytic anemia, non-regenerative (refractory anemia) or be associated with SCD. Myelogram shows a rich marrow with morphological abnormalities of the 3 lines, reflecting the dysmyelopoiesis and maturation disorders. Evolution is the pancytopénique fashion or to acute leukemia.
• bone marrow infiltration
– Any malignancy invading the bone marrow is responsible for pancytopenia where thrombocytopenia is common.These are acute leukemias, malignant lymphomas, Hodgkin’s disease, chronic lymphocytic leukemia, Waldenstrom’s disease, myeloma, cancer. Bone marrow infiltration indicates a poor prognosis. Clinical examination revealed a tumor in some cases syndrome. Thrombocytopenia can be associated with leukemic proliferation objectified from the count, or be part of an overall pancytopenia reflecting on bone marrow infiltration count of neoplastic process. Diagnosis is achieved by the bone marrow aspirate and bone marrow biopsy.
– Some hematopoietic forms of tuberculosis can result in pancytopenia. The bone marrow biopsy found epithelioid homes and culture of the marrow research tubercle bacilli.
– Hemophagocytic syndrome associated with: severe deterioration of general condition, hepatosplenomegaly and pancytopenia. Myelogram found histiocytic hyperplasia with hemophagocytic engulfing platelets, leukocytes and erythrocytes.
Conclusion:
The diagnosis of thrombocytopenia is oriented by the clinic and simple screening tests. A more detailed analysis based on the bone marrow aspiration and (or) bone marrow biopsy to differentiate central thrombocytopenia peripheral thrombocytopenia. The mucocutaneous hemorrhagic syndrome is not correlated with the degree of thrombocytopenia.The treatment of hemorrhagic syndrome associated with thrombocytopenia is adapted to the etiological diagnosis. If platelet transfusions are needed in the central thrombocytopenia, they can be harmful and (or) ineffective in some peripheral thrombocytopenia. This indication must be installed taking into account the benefit compared to risk. It is usually 1 platelet unit for 10 kg of weight.
Highlights to include:
• Mechanisms of thrombocytopenia are 2 main types: Central thrombocytopenia by disorder production, or thrombocytopenia or device by hyperdestruction distribution anomaly.
• If central thrombocytopenia, megakaryocytic lineage is poorly or not represented on the bone marrow aspiration smears with normal platelet life span.
• In case of peripheral thrombocytopenia, the richness of the megakaryocytic lineage is normal, or even increased, with decreased platelet lifespan.
Strong Points to remember:
• Any thrombocytopenia should be checked by a platelet count on levy citrate or finger, to eliminate false thrombocytopenia before considering the etiological investigations. • The mucocutaneous hemorrhagic syndrome is not always correlated with platelet count, but it is still the fact of thrombocytopenia if platelets are below 50,109 / L.
• The examination, physical examination, routine simple tests are very important to guide the diagnostic process.