Platelets Disorders: Causes, Diagnosis, and Treatment

Platelets disorders Presented by Dr. Sahar Gamal Elbager Assistant Professor of Haematology UMST  Platelets disorders Haemorrhagic disorders caused by platelet abnormalities are usually due to quantitative defect (thrombocytopenia), or due to a qualita...

Platelets disorders Presented by Dr. Sahar Gamal Elbager Assistant Professor of Haematology UMST  Platelets disorders Haemorrhagic disorders caused by platelet abnormalities are usually due to quantitative defect (thrombocytopenia), or due to a qualitative defect (platelet function disorders). 25/4/2022 Dr.Sahar Elbager 2  Thrombocytopenia Causes of thrombocytopenia: 1. Failure of platelet production 2. Increased consumption/destruction of platelets 3. Abnormal distribution of platelets 4. Dilution effect 25/4/2022 Dr.Sahar Elbager 3  Failure of platelet production 1. Selective megakaryocyte depression: Rare congenital defects(May-Hegglin anomaly and Wiskott-Aldrich syndrome) Drugs, chemicals, viral infections(CMV,EPV) 2. Part of general bone marrow failure: Cytotoxic drugs,radiotherapy,aplastic anaemia Leukaemia,myelodysplastic syndromes, Myelofibrosis, anaemia and HIV infection 25/4/2022 Dr.Sahar Elbager 4 Failure of platelet production Diagnosis of these causes of thrombocytopenia is made from 1. The clinical history 2. Peripheral blood count 3. The blood film and 4. Bone marrow examination. 25/4/2022 Dr.Sahar Elbager 5  Increased consumption/destruction of platelets Immune-mediated: 1. Idioapthic(ITP) 2. Drug-induced 3. Infections 4. Post-transfusion purpura Thrombocytopenia Non-immune mediated: 1. DIC 2. TTP 25/4/2022 Dr.Sahar Elbager 6  Autoimmune (idiopathic) thrombocytopenic purpura Autoimmune (idiopathic) thrombocytopenic purpura (ITP) may be divided into chronic and acute forms. Acute idiopathic thrombocytopellic purpura This is most common in children. In approximately 75% of patients the episode follows vaccination or an infection such as chickenpox or infectious mononucleosis. 25/4/2022 Dr.Sahar Elbager 7  Autoimmune (idiopathic) thrombocytopenic purpura Spontaneous remissions are usual but in 5-10% of cases the disease becomes chronic (lasting >6 months). 25/4/2022 Dr.Sahar Elbager 8  Autoimmune (idiopathic) thrombocytopenic purpura The diagnosis is one of exclusion and there is debate as to the need for bone marrow aspiration. If the platelet count is over 30 x 10 9 /L no treatment is necessary unless the bleeding is severe. Those with counts below 20 x109 /L may be treated with steroids, especially if there is significant beeding. Dr.Sahar Elbager 9  Chronic idiopathic thrombocytopenic purpura This is a relatively common disorder. The highest incidence has been considered to be in women aged 15-50 It is the most common cause of thrombocytopenia without anaemia or neutropenia. It is usually idiopathic but may be seen associated with other diseases such as systemic lupus erythematosus (SLE), (HIV) infection, CLL, Hodgkin's disease or autoimmtme haemolytic anaemia 25/4/2022 Dr.Sahar Elbager 10  Pathogenesis Platelet autoantibodies are usually IgG. The antibody is directed against antigen sites on the glycoprotein (GP) The normal lifespan of a platelet is 7-10 days but in ITP this is reduced to a few hours. Total megakaryocyte mass and platelet turnover are increased in parallel to approximately five times normal. 25/4/2022 Dr.Sahar Elbager 11  Pathogenesis 25/4/2022 Dr.Sahar Elbager 12  Clinical features Easy bruising In women, menorrhagia. Mucosal bleeding (e.g. epistaxes or gum bleeding) occurs in severe cases 25/4/2022 Dr.Sahar Elbager 13  Diagnosis 1. The platelet count is usually 10-50 x 10 9 L. 2. Hb concentration and WBCs are normal unless there is iron deficiency anaemia because of blood loss. 3. The blood film shows reduced numbers of platelets 4. The bone marrow shows normal or increased numbers of megakaryocytes. 5. Sensitive tests able to demonstrate specific anti- glycoprotein GPlIb or GPIb antibodies on the platelet surface or in the serum in most patients. 25/4/2022 Dr.Sahar Elbager 14  Treatment The aim of treatment should be to maintain a platelet count above the level at which spontaneous bruising or bleeding occurs with the minimum of intervention. In general, a platelet count above 50 x 10 9 /L does not require treatment. 1. Corticosteroids 2. Splenectomy 3. immunosuppressive druds 25/4/2022 Dr.Sahar Elbager 15  Non Immune 1.Disseminated intravascular coagulation Thrombocytopenia may result from an increased rate of platelet destruction through consumption of platelets because of their participation in DIC. 25/4/2022 Dr.Sahar Elbager 16  Non Immune 2.Thrombotic Thrombocytopenic Purpura(TTP) Congenital or acquired form. More in women than in men. There is deficiency of a ADAMTS13 metalloprotease which breaks down ultra large von Willebrand factor multimers (ULVWF), ULVWF are anchored to the endothelial cells, platelets adhere via their GPIb receptors. Increasing platelet aggregation onto the ULVWF multimeric has the potential to form large, occlusive, platelet tluombi. Platelet aggregation result in low count in circulation. 25/4/2022 Dr.Sahar Elbager 17  Thrombotic Thrombocytopenic Purpura(TTP) 25/4/2022 Dr.Sahar Elbager 18  Diagnosis 1. Coagulation tests are normal in contrast to the findings in DIC. 2. ADAMTS13 is absent or severely reduced in plasma. Treatment is with plasma exchange, using fresh frozen plasma (FFP) or cryosupernatant 25/4/2022 Dr.Sahar Elbager 19 Qualitative Platelets Disorders  Platelet function disorders There are many different kinds of platelet function disorders. They can be divided into two categories: A) Hereditary disorders (they run in the family) B)Acquired disorders (meaning they are caused by other diseases or the use of medications. 25/4/2022 Dr.Sahar Elbager 21  A)Hereditary platelet function disorders Hereditary platelet function disorders may produce defectsat each of the different phases of the platelet reactions leading to the formation of the haemostatic platelet plug. 25/4/2022 Dr.Sahar Elbager 22  Bernard-Soulier syndrome In this disease the platelets are larger than normal and there is a deficiency of GPIb (chromosome 22). There is defective binding to VWF, defective adherence to exposed subendothelial connective tissues There is a variable degree of thrombocytopenia. 25/4/2022 Dr.Sahar Elbager 23  Platelet interaction 25/4/2022 Dr.Sahar Elbager 24  Bernard-Soulier syndrome The disorder is often first noticed during childhood. Children have frequent bruises, nose bleeds and bleeding in the mouth and gums. Some may experience gastrointestinal bleeding (bleeding in the gut). Women may experience heavy menstrual bleeding, ( menorrhagia.) 25/4/2022 Dr.Sahar Elbager 25  Bernard-Soulier syndrome Lab. Diagnosis: Prolonged bleeding time. low platelet count platelets appear larger than normal when seen through a microscope platelets do not clump together in response to ristocetin. 25/4/2022 Dr.Sahar Elbager 26  Glanzmann's disease This autosomal recessive disorder leads to failure of primary platelet aggregation because of a deficiency of membrane GPIIb (gene on chromosome 17). It usually presents in the neonatal period and, characteristically, platelets fail to aggregate in vitro to any agonist except ristocetin. 25/4/2022 Dr.Sahar Elbager 27  Platelet interaction 25/4/2022 Dr.Sahar Elbager 28  Glanzmann's disease Lab. Diagnosis: bleeding time is much longer than normal the platelets do not clump together at all (platelet aggregation is absent) 25/4/2022 Dr.Sahar Elbager 29  (B)Acquired platelet function disorders Platelet function can be affected by common drugs. These are: Aspirin (ASA) and other drugs containing aspirin Non-steroidal anti-inflammatory drugs like ibuprofen. 25/4/2022 Dr.Sahar Elbager 30  Other drugs can also affect platelet These include: Some antibiotics Heart drugs Blood thinners Antidepressants Anaesthetics Antihistamines Platelet function returns to normal when these medications are stopped. 25/4/2022 Dr.Sahar Elbager 31