F2I: QUANTI DISORDERS OF PRIMARY HEMOSTASIS PLT DISORDERS

• PATHOPHYSIOLOGIC PROCESS THAT RESULT IN THROMBOCYTOPENIA

  Decreased Platelet Production

  Increased Platelet Destruction

  Abnormal Platelet Distribution
• 2 CATEGORIES IN ABNORMAL PLATELET PRODUCTION

  1. Megakaryocyte Hypoplasia
  2. Ineffective Thrombopoiesis
• MYH9- related Thrombocytopenia Syndromes 


  mutations in the MYH9 gene
• Thrombocytopenia with Absent Radius (TAR)


  RC

  • Associated with the mutation in the RBM8A – CH 1
  • Rare disease, first identified in 1959
  • Platelet count is approximately 10-30 X 103/uL

  
  

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  • Serum TPO levels = normal
  • marrow cellularity = normal or increased.
  • platelet transfusion
• Congenital Amegakaryocytic Thrombocytopenia (CAMT)

  
  

  • RECESSIVE, CONGENITAL
  • Mutation in the MPL gene –ch 1 – loss of TPO receptor
  • Family history is negative, both parents having normal platelet counts and function
  • Markedly elevated serum thrombopoietin
• Group CAMT I


  more severe type of thrombocytopenia with constantly low platelet count and an early onset of pancytopeni
• Group CAMT II


  transient increased in platelet counts during the first year of life and a later or no development of pancytopenia.
• ANKRD26 - RT

  • Mutation on ANKRD26 –Ch 10- incomplete megakaryocyte differentiation
  • 20,000 to 100000/uL or a history of increased bruisability is apparent on early life.
• Wiskott-Aldrich Syndrome


  
  

  • Originally described in 1937, is now known as X-linked hereditary disorder associated with combined immunodeficiency thrombocytopenia, small platelets, eczema and an increased risk to autoimmune disorders and cancer
• NEONATAL THROMBOCYTOPENIA


  • Platelet count less than 150,000 /ul
  • Cause of Neonatal Thrombocytopenia :
  • Infection with toxoplasma , rubella, cytomegalovirus, herpes Thrombocytopenia may be severe platelet count of 70,000 /ul
  • CMV most common infectious agent
• IMPAIRED OR DECREASED PLATELET PRODUCTION


  1. MYH9- related Thrombocytopenia Syndromes
  2. Thrombocytopenia with Absent Radius (TAR)
  3. Congenital Amegakaryocytic Thrombocytopenia (CAMT)
  4. thrombocytopenia 2 (THC2) 
  5. Wiskott-Aldrich Syndrome
  6. Neonatal Thrombocytopenia
• INCREASED PLATELET DESTRUCTION


  • Acute and Chronic ITP
  • Drug Induced immunologic
  • Heparin Induced Thrombocytopenia
  • Neonatal Alloimmune ( isoimmune neonatal) thrombocytopenia
  • Post-transfusion isoimmune thrombocytopenia
  • Secondary autoimmune thrombocytopenia
• IDIOPATHIC THROMBOCYTOPENIC PURPURA


  • A.K.A immune thrombocytopenic purpura (ITP)
  • One of the most common disorders causing severe isolated thrombocytopenia
  • Caused by an autoantibody to the patient’s platelet
  • No specific test to confirm presence of ITP rather diagnosis of exclusion Can be present in children and adults
• ACUTE / CHILDHOOD ITP


  • develops acute with a 1 to 3 weeks duration, usually with bruising or petechiae
  • Present an initial platelet count of less than 20 X 109/L
  • Self-limiting, spontaneous remissions with or without therapy in majority of the patient
  • IgG and corticosteroids are often used to decrease the period of thrombocytopenia
• CHRONIC / ADULT ITP


  • Commonly presents in the 20-50 year old groups, chronic disease process with a greater predilection for women
  • Platelet counts are typically less than 30 X 109/L in patients who present with bleeding manifestations
  • Patient present with mucosal bleeding typical of a primary hemostatic defect, such as menorrhagia, epistaxis, easily bruised, or petechiae
  • IVIG treatment of choice
• DRUG-INDUCED IMMUNE THROMBOCYTOPENIA


  • Appears more frequently in the elderly due to increased usage of medication
  • Purpura occurs approximately 7 days after initial use of the drug but may occur within 3-5 days owing to anamnestic response
• Drug most frequently cited

  1. quinine
  2. quinidine
  3. salicylates
  4. thiazides
  5. sulfa drugs
• Quinine


  one of the most frequent causes of drug-induced thrombocytopenia; where it act as a hapten
• NEONATAL ALLOIMMUNE / ISOIMMUNE NEONATAL THROMBOCYTOPENIA


  • It result to from immunization of the mother by fetal platelet antigen and placental transfer of maternal antibody
  • It is most often caused by maternal alloantibodies to the P1A1 antigen
• NEONATAL AUTOIMMUNE THROMBOCYTOPENIA

  - passive transplacental transfer of abs from mother with ITP or SLE
• POST TRANSFUSION PURPURA

  • Rare disorder
  • containing products. Manifested by rapid onset of severe thrombocytopenia
• QUANTITATIVE PLATELET DISORDER SECONDARY (NON IMMUNE)


  1. Thrombocytopenia in Pregnancy
  2. HIV Infection
  3. HDN
  4. TTP
  5. DIC
  6. Drug induced
• THROMBOCYTOPENIA IN PREGNANCY AND PREECLAMPSIA

  • Gestational Thrombocytopenia
  • Platelet count : 100,000 -150,000/ul
  • Connection with thrombocytopenia, in an manner that blood coagulation is activated and is detected by elevated FDG and thrombin-antithrombin process
  • Low level of ADAMTS13 is detected
• Preeclampsia


  defined by hypertension and proteinuria; usually becomes evident during second trimester and is a major contributor to maternal and fetal morbidity and mortality
• Eclampsia


  defined by the occurrence of acute neurologic abnormalities in a preeclamptic woman during peripartum period
• HELLPS SYNDROME


  • Disorder related to preeclampsia/eclampsia and is seen in the peripartum period and defined by the presence of microangiopathic HA, elevated liver enzymes, and low platelet count
  • HELLP (Hemolysis, Elevated liver enzymes, Low platelet count)
  • HELLP is difficult to differentiate from: TTP DIC HUS
• GESTATIONAL THROMBOCYTOPENIA


  • Mild thrombocytopenia with platelet counts of 50-80 X 109/L
  • Commonly develops in the *3rd trimester* of pregnancy and does not cause bleeding in the mother or infant
  • Low platelet count returns to normal after deliver
• HIV RELATED THROMBOCYTOPENIA


  • Appears to be correlated between CD4+ T cell depletion, viral load in plasma and the occurrence of thrombocytopenia
  • Development of marrow fibrosis and marrow involvement by AIDS-related lymphoma may also lead to thrombocytopenia
  • Intravenous IgG and anti-D globulin are found to be effective treatment
• THROMBOTIC THROMBOCYTOPENIC PURPURA


  • First described as a pentad of signs and symptoms that include: thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic abnormalities and renal dysfunction
  • Hyaline microthrombi are the characteristic pathologic feature and are found in multiple organs
  • Coagulation screening tests and D-Dimer assay are NORMAL in TTP, in contrast to DIC which they are abnormal
  • Two types of TTP: Acquired and hereditary
• ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA

  • Associated with ADAMTS13 deficiency (a disintegrin-like and metalloprotease with thrombospondin motifs) and is found in most cases.
  • ADAMTS13 is also decreased in sepsis, DIC, and liver disease
  • Thrombi found most extensively in the heart, pancreas, spleen, kidney, adrenal gland and brain and are composed mainly of platelets and vWF
• HEREDITARY THROMBOTIC THROMBOCYTOPENIC PURPURA


  • Also known as Schulman-Upshaw syndrome or Chronic Relapsing TTP
  • Rare disorder believed to < 1% of the TTP cases
  • In the typical cases, the affected neonate is born with meconium stain or presents within a few hours after birth with neonatal distress, jaundice and thrombocytopenia
  • Hemolysis with schistocytes on blood smears may be noted
  • Hereditary TTP responds to 10-15 mL of FFP per kilogram of body weight administered every 2 to 3 weeks
• DISSEMINATED INTRAVASCULAR COAGULATION


  DIC appears to be accelerated platelet destruction in combination with coagulation factors consumption

  
  

  • Acute - Rapid platelet consumption
  • Chronic – Low grade consumptive coagulopath
• DISSEMINATED INTRAVASCULAR COAGULATION


  • Caused by many illnesses, sepsis, obstetric emergencies and severe trauma, and may cause bleeding
  • Chronic form may be seen in cancer and may result in thrombosis rather than bleeding
  • Thrombocytopenia is usually seen in acute DIC
  • Platelet count may be normal or elevated in chronic DIC
  • appears to be accelerated platelet destruction in combination with coagulation factors consumption
• ABNORMALITIES IN DISTRIBUTION OR DILUTION

  1. Splenic sequestration
  2. Kasabach-Meritt syndrome
  3. Hypothermia
  4. Loss of Platelets : massive blood transfusion
• SPLENOMEGALY


  • May lead to thrombocytopenia by inducing a reversible pooling up to 90% of total body platelets
  • Platelet production is usually normal
  • Chronic liver disease with portal hypertension and congestive splenomegaly
  • Most common disorder causing thrombocytopenia
• HYPERSPLENISM


  It is distinguished from uncomplicated splenomegaly in that pooling is accompanied by increased destruction of platelets, leukocytes and erythrocytes in association with increased marrow precursors of the deficient and correction of the cytopenia by splenectom
• KASABACH-MERRITT SYNDROME


  • Profound thrombocytopenia related to platelet trapping within a vascular tumour, either a Kaposi-like hemangioendothelioma or a tufted angioma
  • Thrombocytopenia is usually severe and associated with DIC
  • Contributing factors include “platelet trapping” and platelet consumption associated with DIC.
  • Platelet trapping demonstrated by immunohistochemical staining of the tumours with anti-CD61 antibodies
• Thrombocytosis


  characterized by an increase in the circulating platelet count greater than 450,000/uL. The result of primary bone marrow disorder

  
  

  • Hodgkin’s disease
  • Polycythemia vera
  • Myelofibrosis
  • CML
  • Thrombocythemia
• Reactive/ Secondary thrombocytosis


  a secondary response most associated with the following disorders:

  1. IDA associated with chronic blood loss
  2. Chronic inflammatory disease may be associated with high platelet counts.
  3. Splenectomy-associated thrombocytosis
  4. Rebound thrombocytosis, which may occur after a platelet depletion through a massive blood loss.

  • TPO levels in plasma are decreased
  • Promoted by different types of drug like epinephrine, recombinant IL11 (Oprevelkin)
• CH 1

  Chromosome no. involve with px prob in thrombopoeitin