Pathology hematology 3

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Pathology hematology 3

  1. 1. Sickle cell anemia Hemolytic anemia
  2. 2. Sickle cell anemia <ul><li>Hereditary HA </li></ul><ul><li>Hb disorder (Hemoglobinopathy) </li></ul><ul><li>Abnormal HbS is common in Africa, India and among the Blacks in US </li></ul><ul><li>Rare in Caucasian and Asian races </li></ul><ul><li>The onset: early in infancy (HbS replace HbF)  death occurred during early adult life </li></ul><ul><li>Improvements in management  pts survive longer </li></ul><ul><li>Two phenotypes: </li></ul><ul><li>Sickle cell trait – heterozygous (A/S) vs </li></ul><ul><li>Sickle cell ds. – homozygous (S/S) </li></ul>
  3. 3. <ul><li>Normal: HbA </li></ul><ul><li>A single point mutation in beta-chain </li></ul><ul><li>Codon 6 (G A G  G T G = Glutamic acid to Valine)  HbS </li></ul><ul><li>Tendency to polymerization, yielding semisolid crystalline structures  TACTOIDs </li></ul><ul><li>TACTOIDs: </li></ul><ul><li>1-  Hb solubility </li></ul><ul><li>2- Change RBC shape </li></ul><ul><li>3-  Deformability of RBC </li></ul>Pathology
  4. 4. Clinical features: <ul><li>Chronic extravascular hemolysis </li></ul><ul><li>Severe anemia </li></ul><ul><li>Growth retardation (common) </li></ul><ul><li>Mild hemolytic jaundice – absent urinary bilirubin &  fecal & urinary urobilinogen </li></ul><ul><li>Bone marrow: normoblastic hyperplasia – leading to expansion of the marrow cavity in bones an causing bony deformities (tower skull and hair-on-end appearance on skull x-rays) </li></ul><ul><li>Chronic leg ulcers – unknown pathogenesis </li></ul>
  5. 5. Frontal Bossing X-ray: ‘Hair-on-end’ skull Chronic leg ulcer
  6. 7. Diagnosis: <ul><li>Peripheral blood smear – sickle cells </li></ul>Sickle cells Normal RBC
  7. 8. 2. Hb electrophoresis – Identification & quantification of HbS (80% Hbs, absence of HbA; HbF & HbA 2 variably increased)
  8. 10. <ul><li>Molecular techniques – </li></ul><ul><li>Mutation detection in the gene causing SC condition (supplementary test) </li></ul><ul><li>Single mutation in β-globin gene </li></ul><ul><li>DNA probe - limited to prenatal diagnosis </li></ul>
  9. 11. Complications: <ul><li>Aplastic crisis – sudden failure of hematopoeisis in BM </li></ul><ul><li>Hemolytic crisis – unknown cause, characterized by a sudden  hemolysis </li></ul><ul><li>Hemosiderosis & secondary hemosiderosis – common in long-term survivor, stimulation iron absorption in the intestine due to chronic erythroid hyperplasia & blood transfusions </li></ul><ul><li>Vaso-occlusive crisis – plugging of microcirculation (aggregates of sickle cells) </li></ul><ul><li>Splenic changes: </li></ul><ul><li>Early childhood – slightly enlarged due to RE hyperplasia </li></ul><ul><li>Adults – SC ds.  shrunken & contain *Gamna-Gandy bodies, systemic infection by encapsulated bacteria (Pneumococcal bacterimia & Salmonella osteomyelitis </li></ul><ul><li>- SC trait  without symptom </li></ul>*Gamna Gandy nodules / siderotic nodules / fibrosiderotic nodules
  10. 12. An enlarged spleen due to splenic sequestration crisis in a patient with sickle anemia
  11. 13. Sickle cells are seen in splenic red pulp in a case of splenic sequestration crisis.
  12. 14. Kidney: Hemosidrin deposit LIVER: HEMOSIDEROSIS Hemosiderin deposits
  13. 15. Alloimmune/ Isoimmune: 1) Hemolytic Transfusion Reaction 2) Hemolytic Disease of the Newborn Hemolytic anemia RBCs are lysed as a result of the action of antibodies of another individual
  14. 16. Hemolytic Transfusion Anemia <ul><li>Transfusion if incompatible blood – ABO incompatibility, rarely due to other blood gp. </li></ul><ul><li>Typically cause acute hemolytic reaction </li></ul><ul><li>Severe form – produce intravascular hemolysis, occurs within minutes to hours  shock  death </li></ul><ul><li>Less severe – produce extravascular hemolysis  delayed hemolytic reaction </li></ul><ul><li>The transfused (donor) RBCs are destroyed by antibody present in the recipient’s plasma </li></ul><ul><li>ABO hemolytic transfusion reaction avoided by ABO grouping </li></ul>
  15. 17. Hemolytic Disease of the Newborn <ul><li>Clinically significant caused by Rh incompatibility, rarely due to ABO incimpatibility </li></ul><ul><li>Rh system is complex – consists of 3 pairs of alleles ( D, d, C, c, E, e ), produces variety of phenotypes </li></ul><ul><li>Allele D is the strongest antigen, routinely tested </li></ul><ul><li>Rh +ve or Rh –ve: to denote the presence or absence of D antigen </li></ul><ul><li>Anti-Rh antibodies: </li></ul><ul><li>Rh –ve  doesn’t have natural anti-Rh antibodies, may develop immune anti-Rh antibodies (IgG) if RBC with Rh+ve enter the circulation (blood transfusion or pregnancy) </li></ul><ul><li>Effect on fetus: Intrauterine death or hemolytic ds of newborn </li></ul><ul><li>Prevention: </li></ul><ul><li>Accurate Rh typing </li></ul><ul><li>Administration of high dose of Rh antibody (Rogham) to an Rh-ve woman during childbirth or abortion </li></ul><ul><li> Avoid sensitizing Rh-ve women </li></ul>
  16. 18. Hemostatic disorders
  17. 19. Normal vascular system <ul><li>Blood vessels – vasoconstriction </li></ul><ul><li>Platelets – form hemostatic plug & permanent thrombus </li></ul><ul><li>Blood coagulation </li></ul><ul><li>Fibrinolysis </li></ul><ul><li>Disturbance of any one of these mechanism may produce abN bleeding or abN thrombus </li></ul><ul><li>Clinical effects are similar regardless of the mechanism </li></ul>
  18. 20. Vascular defects <ul><li>The most common cause of bleeding diathesis </li></ul><ul><li>Certain vascular disorder: abN collagen or elastin </li></ul><ul><li>Henoch-Schönlein purpura </li></ul><ul><li>Hereditary hemorrhagic telangiectasia </li></ul>
  19. 21. Henoch-Schönlein purpura <ul><li>Poststreptococcal ds in childhood </li></ul><ul><li>Occurs1-3 weeks after streptococcal infection </li></ul><ul><li>Mediated by deposition of cross-reaction IgA or immune complexes + complement on the endothelial </li></ul><ul><li>Clinical features: Purpura, abdominal pain, arthralgia/ arthritis, glomerulonephritis, fever </li></ul><ul><li>Prognosis - based on renal lesion </li></ul>
  20. 22. Hereditary hemorrhagic telangiectasia <ul><li>Hereditary: autosomal dominant trait </li></ul><ul><li>Manifested by multiple capillary microaneurysms in the skin & mucous membranes </li></ul><ul><li>Lesions – become more conspicious with age & fragile </li></ul><ul><li>Predisposing to episodes of acute severe bleeding & chronic blood loss from the intestinal tract </li></ul><ul><li>Results in Iron def. Anemia </li></ul>
  21. 23. Platelets <ul><li>Anuclated cytoplasmic fragments </li></ul><ul><li>Derived from megakaryocytes </li></ul><ul><li>Normal count = 150,000 – 400,000/μL </li></ul><ul><li>Peripheral blood smear: small granular cytoplasmic fragment, ¼RBC size </li></ul><ul><li>Main function: HEMOSTASIS </li></ul><ul><li>Abnormalities: </li></ul><ul><li>Thrombocytopenia (  ) </li></ul><ul><li>Thrombocytosis (  ) </li></ul><ul><li>AbN platelet fx. </li></ul>
  22. 24. Idiopathic Thrombocytopenic Purpura (ITP) <ul><li>Severe reduction of platelet no. </li></ul><ul><li>Caused by immune destruction of platelets </li></ul><ul><li>Pathology: </li></ul><ul><li>Platelet survival is impaired </li></ul><ul><li>Platelet count is markedly  </li></ul><ul><li>BM – increased megakaryocytes </li></ul><ul><li>Spleen – major sites of destruction of antibody-coated platelets </li></ul><ul><li>Bleeding time is prolonged &  capillary fragility </li></ul><ul><li>Test of coagulations are N </li></ul>
  23. 25. <ul><li>Acute ITP: </li></ul><ul><li>Mainly seen in children </li></ul><ul><li>50% of the cases assoc. with history of viral inf. 2-3 weeks before infection </li></ul><ul><li>Immune complexes bind to the surface of platelet </li></ul><ul><li>Phagocytosis by splenic macrophages </li></ul><ul><li>Spontaneous recovery in the majority of pts, 80% are normal after 6 months </li></ul>
  24. 26. <ul><li>Chronic ITP: </li></ul><ul><li>Mainly in adults </li></ul><ul><li>With a predilection for female (3:1) </li></ul><ul><li>Frequent relapse occurrence during pregnancy </li></ul><ul><li>Thrombocytopenia due to peripheral destruction of platelets </li></ul><ul><li>IgG antiplatelet autoantibody on the platelet surfaces </li></ul><ul><li>Multiple relapses & remissions </li></ul><ul><li>Neonatal TP: </li></ul><ul><li>Occurs in children born to mothers with chronic ITP </li></ul><ul><li>Transfer of the IgG antibodies across the placenta </li></ul>
  25. 27. Clinical features & Treatment: <ul><li>Bleeding tendency </li></ul><ul><li>Purpura </li></ul><ul><li>Bleeding from mucosal surface – hematuria, melena, menorrhagia & hemoptysis </li></ul><ul><li>Treatment with  dose corticosteroids –suppress splenic phagocytic activity </li></ul><ul><li>Splenectomy – removal of main site of platelet destruction </li></ul>
  26. 28. Disorder of blood coagulation <ul><li>Etiology: </li></ul><ul><li>Def. of coagulation factors </li></ul><ul><li>Presence of circulating anticoagulants </li></ul><ul><li> Fibrinolytic activity </li></ul><ul><li>Clinical features: </li></ul><ul><li>Tend to bleed excessively </li></ul><ul><li>Severe cases: spontaneous bleeding </li></ul><ul><li>Usual bleeding & persistent </li></ul>
  27. 29. Factor VIII Def. <ul><li>Factor VIII coagulant (VIII:c) – critical component of intrinsic coagulation pathway </li></ul><ul><li>aka as antihemophilic globulin def. </li></ul><ul><li>Factor VIII:c – measured by bioassay or immunoassay </li></ul><ul><li>Hemophilia A </li></ul><ul><li>Von Willebrand’s ds. </li></ul>
  28. 30. Hemophilia A <ul><li>Inherited as X-linked recessive trait </li></ul><ul><li>Mainly in males </li></ul><ul><li>Female: both abN gene on X-chromosome (homozygous) </li></ul><ul><li>Pts has less than 1% factor VIII coagulant activity </li></ul><ul><li>Spontaneous bleeding </li></ul><ul><li>Partial Thromboplastin Time (PTT) test is prolonged </li></ul><ul><li>Significant  factors VIII activity </li></ul><ul><li>Treatments: maintain plasma factor VIII activity, cryopercipitate (lyophilized factor VIII concentrate pooled from plasma of large number of blood donors) </li></ul>
  29. 32. Von Willebrand’s Ds. <ul><li>Autosomal dominant </li></ul><ul><li>Def. of entire circulating factor VIII complex </li></ul><ul><li>Both factor VIII & Von Willebrand factor  to the same extent </li></ul><ul><li>Clinically, pts show bleeding after minor trauma </li></ul><ul><li>Onset symptoms is in childhood, but may  with age </li></ul><ul><li>Common sites of bleeding: skin (easy bruising) & mucous membrane (epistaxis) </li></ul><ul><li>Dx: Prolonged PTT,  factor VIII coagulant activity,  Von Willebrand factor, Prolonged bleeding time </li></ul>
  30. 33. Factor IX Def. <ul><li>Christmas ds; Hemophilia B </li></ul><ul><li>Uncommon </li></ul><ul><li>Results from def. of factor IX </li></ul><ul><li>X-linked recessive </li></ul><ul><li>Greater prevalence in males </li></ul><ul><li>Clinical picture – identical to hemophilia A </li></ul><ul><li>Dx is made when factor VIII activity is N </li></ul><ul><li>Plasma factor IX assay – greatly  </li></ul><ul><li>Treatment: Fresh plasma or factor IX concentrate </li></ul>

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