Haemorrhagic and Haemolytic of Newborn Diseases


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actually for haemorrhagic newborn diseases, mainly focus of vit K def...the other is for revision n more commonly occur in child n adults....for haemolytic newborn disease, mainly focus on Rh disease n ABO incompatibility.....the other when childhoods

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Haemorrhagic and Haemolytic of Newborn Diseases

  1. 1. Haemorrhagic & Haemolytic Disease in Newborn
  2. 2. Normal Haemostasis5 main components:1) Coagulation factors- activated when released of Tissue Factor (TF) by vessel injury2) Coagulation inhibitors- to prevent widespread coagulation3) Fibrinolysis- limits fibrin deposition4) Platelets- aggregate at sites of vessel injury to form primary haemostatic plug5) Blood vessels- intact vascular endothelium secretes PGI2 and NO which promote vasodilation & inhibit plt aggregation. Damaged endothelium releases TF & procoagulants (collagen & vWF).
  3. 3. Endpoint of coagulation cascade is generation of thrombin.
  4. 4. Abnormal bleeding
  5. 5. Acquired disorders of coagulationSecondary toi. Vit K def.ii. Liver diseaseiii. ITP ( immune thrombocytopenia)iv. DIC ( disseminated intravascular coagulation)
  6. 6. 1) Vit. K deficiency• Essential for production of active forms of factors II, VII, IX, X and anticoagulants such as protein C & S• Def d/t – Inadequate intake – Malabsorption ( coeliac dz, cystic fibrosis, obstructive jaundice) – Vit K antagonists (eg. Warfarin)
  7. 7. Pathogenesis Conversion of PIVKA to Vit K converted to vit K Non-functional proteins biologically active forms epoxide which cycled called PIVKA (proteins with carboxylation of back to reduced form byformed in vit. K absence) glutamic acid reductases Gamma-carboxylated glutamic acid binds Ca ions which forms a complex with platelet phospholipid
  8. 8. 2) Liver Disease• Biliary obstruction impaired vit K absorption l/t decrease synthesis FII,FVII,FIX and X.• Severe hepatocellular dz, reduced FV, fibrinogen & plasminogen activator.• Dysfunctional fibrinogen (dysfibrinogenaemia)• Low thrombopoietin production l/t thrombocytopenia• Hypersplenism associated with portal HTN l/t thrombocytopenia
  9. 9. • Disseminated intravascular coagulation (DIC) related to release of thromboplastins from damaged liver l/t low conc. of antithrombin, protein C, impaired removal activated clotting factors & increase fibrinolytic activity.
  10. 10. 3) Immune Thrombocytopenia (ITP)• Commonest cause of thrombocytopenia in childhood• Incidence of 4 per 100 000 children per year• Caused by antiplt IgG autoantibodies• Approx. 75% follows vaccination or infect. such as chickenpox• Associated with SLE, HIV, CLL, Hodgkin’s dz or autoimmune haemolytic anemia
  11. 11. Clinical features• Children ages of 2-10 years old• Onsets 1-2 weeks after viral infection• Petechiae• Purpura• Superficial bruising• Epistaxis• Intracranial bleeding (rare)
  12. 12. 4)Disseminated Intravascular Coagulation (DIC)• Coagulation pathway activation l/t diffuse fibrin deposition in microvasculature and consumption of coagulation factors & plts.• Commonest causes are severe sepsis or shock d/t circulatory collapse (in meningococcal septicaemia or extensive tissue damage from trauma or burns.
  13. 13. Pathogenesis Triggered by entry of Increased activity of procoagulant material tissue factor release into circulation eg.from damaged tissues Severe trauma, liver on tumour cells diseaseInitiated by widespread Deposition of fibrin in endothelial damage & microcirculation, collagen exposure eg. intravascular thrombin Severe burns formation Intense fibrinolysis stimulated by thrombi on vascular walls
  14. 14. Combined action of Bleeding probs d/tthrombin & plasmin thrombocytopenia cause depletion of caused by consumption fibrinogen and all of plts coagulation factors
  15. 15. Clinical Features• Bleeding• Generalized bleeding in GIT, oropharynx, into lungs, urogenital tract and vaginal bleeding particularly severe• Skin lesions• Renal failure• Gangrene of toes• Cerebral ischaemia
  16. 16. Inherited diseases1) Haemophilia• Commonest severe inhereted: haemophilia A & haemophilia B• X-linked recessive inheritance• In haemophilia A, there is FVIII deficiency• 1 in 5000 male births• Haemophilia B (FIX def.)• 1 in 30 000 male births
  17. 17. Clinical features• Bleeding episodes most freq. in joints & m/s• Crippling arthritis (recurrent spontaneous bleeding into joints and m/s)• Painful haemarthroses and m/s haematomas l/t progressive joint deformity & disability• Intracranial haemorrhage• Bleeding post-circumsition• Prolonged oozing from heel stick & venepuncture sites• Spontaneous haematuria & GI haemorrhage• Haemophilic pseudotumours
  18. 18. 4) Von Willibrand disease (vWD)• Has 2 major roles: – Facilitates plt adhesion to damaged endothelium – Acts as carrier protein for FVIII:C• Results from either qualitative or quantitaive def. of vWD• l/t defective plt plug formation and def. of FVIII:C• Many different mutations in vWF gene and many types of vWD• Inheritance usually autosomal dominant• Commonest subtype, type I (60-80%)
  19. 19. ClassificationType IQuantitative partial defType IIFunctional abnormalityType IIIComplete def
  20. 20. Clinical features• Bruising• Prolonged, excessive bleeding after surgery• Epistaxis & menorrhagia (mucosal bleeding)• Haematomas & haemarthroses (uncommon)
  21. 21. Hemorrhagic disease of newborn Diagnosis Investigation Treatment Management Azizah Majid HBA 10027653
  22. 22. Notes• Vitamin K represents a group of lipophilic and hydrophobic vitamins. The term vitamin K originated from koagulations-vitamin in German• Vitamin K is a necessary cofactor for γ- glutamyl carboxylase, the enzyme required for posttranslational carboxylation of prothrombin, FVII, FIX, and FX, and proteins C, S, and Z.
  23. 23. Abstract on Haemorrhagic disease in newborn and older infants: a study in hospitalizedchildren in Kelantan, Malaysia. Retrospective study: epidemiology, CF, lab findings, Classical haemorrhagic disease treatment and outcome of of the newborn was the haemorrhagic disease in 42 commonest presentation (48%), Kelantanese infants- Hospital followed by early onset (29%)Universiti Sains Malaysia during a and late onset (24%) disease. 2-year period (1987-1988). Home deliveries accounted for All the infants had prolonged 81% of the affected infants. Commonest presenting CF: prothrombin and partial Most of these babies were not pallor, jaundice, umbilical cord thromboplastin times which given vitamin K at birth in bleeding, tense fontanelle, were corrected by contrast to those delivered in convulsions & hepatomegaly. administration of vitamin K. hospitals.Subdural haemorrhage was the The overall case fatality rate:commonest form of intracranial 14%. The results of this study haemorrhage, followed by :emphasize the value of vitamin subarachnoid haemorrhage. K prophylaxis in the newborn.
  24. 24. DDx of neonatal haemorrhagic disorder Vitamin K Neonatal Platelet DeficiencyThrombocytopenia Abnormalities Bleeding Inherited Coagulation Liver Disease Disorders
  25. 25. Diagnosis• The diagnostic criteria for vitamin K deficiency bleeding include:• Prolonged prothrombin time (PT)/Elevated international normalized ratio (INR) (gold standard)• Prolonged activated partial thromboplastin time (aPTT)• Fibrinogen levels and a platelet count within in normal range for newborns• The diagnosis is confirmed if the INR normalizes after administration of vitamin K and the bleeding is stopped.
  26. 26. Why It Is Done• The prothrombin time (PT) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation ( INR is a calculation made to standardize prothrombin time. INR is based on the ratio of the patients prothrombin time and the normal mean prothrombin time)• PT measures factors I (fibrinogen), II (thrombin), V, VII, and X.• It is used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway• Blood clotting factors: blood to clot (coagulation).• Prothrombin, or factor II, made by the liver. Vitamin K is needed to make it & other clotting factors.The prothrombin time can be prolonged as a result of deficiencies in vitamin K, warfarin therapy, malabsorption, or lack of intestinal colonization by bacteria (such as in newborns). In addition, poor factor VII synthesis (due to liver disease) or increased consumption (in disseminated intravascular coagulation) may prolong the PT.
  27. 27. Tests and Exams• Significant bleeding in neonates should prompt clinical evaluation.• ‘Initial empirical therapy consists of platelet and/or factor supplementation, which is often administered while diagnostic studies are under way’• Laboratory evaluation of the hemorrhage in newborns should include Sepsis evaluation determination of the ( Blood clotting tests) platelet count, PT, aPTT, TT, and fibrinogen concentration.
  28. 28. Cont..IMAGING STUDIES• Ultrasound-intracranial bleeding – rare and usually associated with other causes of bleeding, particularly thrombocytopenia• MRI – exposes the neonate to no radiation – becoming the preferred way to study the brain because tissue damage can be better defined.
  29. 29. Cont..PROCEDURES• If the cause of bleeding is not straight forward, the caregiver may need to perform other procedures like endoscopic retrograde cholangiopancreatography [ERCP] to rule out hepatobiliary diseases.HISTOLOGIC FINDINGS• If liver biopsy is indicated, histopathology with and without special stains or biochemical analyses may be helpful to rule out hepatitis, biliary atresia, tumors, and inherited metabolic diseases of the liver.
  30. 30. Cont…• Genotype analysis(GA) : Congenital vitamin K deficiency is an autosomal recessive disorder that occurs because of mutations in the genes encoding γ-glutamyl carboxylase or vitamin K2,3–epoxide reductase complex. Neonates with this disorder often have severe bleeding, including IntraCranial Haemorrhage. GA to confirm the defect.
  31. 31. Tx & Management• Vitamin K :for prevention of & tx of vit. K deficiency bleeding (VKDB). Other coagulation factors are rarely needed.• Severe bleeding: use of fresh frozen plasma.• No other drugs or treatments are acceptable substitutes for prompt vitamin K dosing.• Subcutaneous administration of vit. K is preferred over the intramuscular (IM) route in symptomatic infants.
  32. 32. Cont…SURGICAL CARE• Normally, vitamin K deficiency bleeding infants do not require surgical care but in rare cases, an infant may need neurosurgical evaluation and treatment.• Other conditions, such as those associated with short bowel syndrome and hepatobiliary disease may require surgical evaluation
  33. 33. Potential Complications• Bleeding inside the skull (intracranial hemorrhage), with possible brain damage• Death• Severe bleeding
  34. 34. Prevention• Many newborns- deficient in vit. K, whether measured in cord blood or indirectly by measuring the levels of vitamin K–dependent coagulation proteins. Recommends giving every baby a shot of vitamin K immediately after birth. This practice has helped prevent the condition.• The early onset form of the disease may be prevented by giving vitamin K shots to pregnant women who take anti-seizure medications.(mechanisms by which anticonvulsant drug l/t vit. K deficiency bleeding in neonates :not clearly understood)• Most infants born to well-nourished mothers have adequate vitamin stores at birth – Vitamin K is naturally produced by intestinal bacteria which newborn’s lack resulting in the deficiency – Suppression of intestinal bacteria by various antibiotics is responsible for this deficiency – Infants receive Vitamin K either orally or intramuscularly
  35. 35. Prognosis (Outlook)• The outlook tends to be worse for babies with late onset hemorrhagic disease than other forms. There is a higher rate of bleeding inside the skull (intracranial hemorrhage) associated with the late onset condition.
  36. 36. RECOMMENDED VALUE• There is no upper limit to vitamin K because of its low toxicity – Infants 0-6 months = 2 µg – Infants 7-12 months = 2.5 µg – Children 1-3 years = 30 µg – Children 4-8 years = 55 µg – Children 9-13 years = 60 µg – Adolescents 14-18 years = 75 µg
  38. 38. • Haemolytic anemia is characterised by reduced red cell lifespan due to increased red cell destruction in the circulation (intravascular haemolysis) or liver/spleen (extravascular haemolysis)• In haemolysis, red cell survival may be reduced to a few days but bone marrow production can increase about 8-fold, so haemolysis only lead to anemia when bone marrow is no longer able to compensate for the premature destruction of red cells
  39. 39. Common causes• RhD incompatibility• ABO incompatibility
  40. 40. Rare causes• Maternal autoimmune disease such as autoimmune hemolytic anemia or systemic lupus erythematosus: maternal antibodies enter fetal circulation and result in fetal or infant erythrocyte destruction• Minor blood group antigen incompatibility (Kell, Duffy, M, S)• Drug-induced hemolysis such as from penicillin or acyclovir• Infection such as from cytomegalovirus, toxoplasmosis, syphilis, or sepsis• Disseminated intravascular coagulation• Hereditary erythrocyte disorders such as hereditary spherocytosis/elliptocytosis, thalassemia, glucose-6- phosphate dehydrogenase deficiency, pyruvate kinase deficiency• Metabolic abnormalities such as acidosis or galactosemia• Angiopathic hemolysis such as cavernous hemangioma, large vessel thrombi, renal artery stenosis, or severe coarctation of the aorta
  41. 41. ISOIMMUNIZATION Rh disease ABO incompatibility
  42. 42. 1. Rh disease• Rhesus disease is a condition which affects an unborn baby when its mother’s immune system generates antibodies which attack the baby’s red blood cells.• Prevalence of genotype varies with the population. Rh negative individuals comprise 15% of Caucasians, 5.5% of African Americans, and <1% of Asians.• For Rh (D) disease to develop in an unborn baby, two conditions must be met. – a woman with the Rhesus-negative blood type is pregnant with a baby who has Rhesus-positive blood. – the pregnant woman must have previously been exposed to Rhesus- positive blood. This second condition must be met in order for the woman’s immune system to generate antibodies to the Rhesus- positive blood cells of the baby.
  43. 43. • Rhesus disease only affects the baby. It will not cause any symptoms for the mother.• In the unborn baby, they may become anemic which can be measured by Doppler ultrasound (blood thinner and flow quickly)• In the newborn baby this may cause: – Anemia with/without jaundice – increased breathing rate – poor muscle tone – poor feeding• Wont always have obvious symptoms when they are born. Symptoms can develop up to three months afterwards.
  44. 44. • If rhesus disease causes severe anemia in the fetus, it can also cause: – fetal heart failure – fluid retention – swelling (oedema) – Stillbirth• In newborn baby: – Kernictus (deafness, blindness, brain damage, learning difficulties, death)
  45. 45. Investigation…• Maternal – Kleihauer-Betke / flow cytometry • Can confirm that fetal blood has pass into maternal circulation • Estimate the amount of fetal blood has passed into maternal circulation – Indirect Coombs test • Screen blood from antenatal women for IgG ab that may pass through the placenta and cause HDN
  46. 46. • Unborn baby – Doppler ultrasound – Fetal blood sampling (FBS)• Newborn baby – Direct Coombs test • Evidence of anti-D ab that have cross placenta – FBC • Hb level and platelet count – Bilirubin
  47. 47. Treatments…• Unborn baby – Intrauterine blood transfusion (IUT)• Newborn baby – Phototherapy – Exchange transfusion – Intravenous immunoglobulin (IVIG) • Prevent destruction of RBC
  48. 48. Preventions…• All non-sensitized Rh D-negative women should be given anti- D immunoglobulin at 28 and 34 weeks of gestation to reduce risk of sensitization from fetomaternal haemorrhage.• At birth, if the baby is Rh –ve, no further treatment needed.•• If baby is Rh +ve, prophylactic anti-D should be administered within 72h of delivery.
  49. 49. 2. ABO Incompatibility• ABO incompatibility is the most common cause of hemolytic disease of the newborn.• Approximately 15% of live births are at risk, but manifestations of disease develop in only 0.3-2.2%.
  50. 50. 2. ABO Incompatibility• With maternal blood types A and B, isoimmunization does not occur because the naturally occurring antibodies (anti-A and -B) are IgM, not IgG.• In type O mothers, the antibodies are predominantly IgG, cross the placenta and can cause hemolysis in the fetus.• The association of a type A or B fetus with a type O mother occurs in ~15% of pregnancies. However, HDN occurs in only 3%, is severe in only 1%, and <1:1,000 require exchange transfusion.• Unlike Rh, ABO disease can occur in first pregnancies, because anti-A and anti-B antibodies are found early in life from exposure to A- or B-like antigens present in many foods and bacteria.• Clinical presentation: generally less severe than with Rh disease.
  51. 51. • Diagnosis and investigation are same as Rh disease.• Treatment are by phototherapy and exchange transfusion.• There is no effective prevention against ABO incompatibility reaction.
  52. 52. Differential diagnosis• Hemorrhage in the newborn• Failure of erythrocyte production in the newborn• Conjugated hyperbilirubinemia
  53. 53. AUTOIMMUNE HEMOLYTIC ANEMIAanemia secondary to prematuredestruction of red blood cells (RBCs)caused by the binding of autoantibodiesand/or complement to RBCs
  54. 54. ISOIMMUNE VS AUTOIMMUNE• The most important immune hemolytic disorder in pediatric practice is hemolytic disease of the newborn (erythroblastosis fetalis), caused by transplacental transfer of maternal antibody active against the RBCs of the fetus, that is, isoimmune hemolytic anemia• Various other immune hemolytic anemias are autoimmune
  55. 55. Pathogenesis• abnormal antibodies are directed against RBC membrane antigens, but the pathogenesis of antibody induction is uncertain.• The autoantibody may be produced as an inappropriate immune response to an RBC antigen or to another antigenic epitope similar to an RBC antigen, known as molecular mimicry.• Alternatively, an infectious agent may alter the RBC membrane so that it becomes “foreign” or antigenic to the host. The antibodies usually react to epitopes (antigens) that are “public” or common to all human RBCs, such as Rh proteins.
  56. 56. AIHA• caused by autoantibody-induced hemolysis (the premature destruction of circulating red blood cells); – usually idiopathic, – SECONDARY, associated with 1. infection, 2. lymphoproliferative disorders, 3. autoimmune diseases 4. drugs
  57. 57. CLASSIFICATION• Based on etiology: – Warm antibody mediated: immunoglobulin (Ig) G (often idiopathic or associated with leukemia, lymphoma, thymoma, myeloma, viral infections, and collagen-vascular disease) – Cold antibody mediated: IgM and complement in majority of cases (often idiopathic; at times associated with infections, lymphoma, or cold agglutinin disease) – Drug induced: three major mechanisms: 1. Antibody directed against Rh complex (e.g., methyldopa) 2. Antibody directed against RBC-drug complex (hapten induced; e.g., penicillin) 3. Antibody directed against complex formed by drug and plasma proteins; the drug-plasma protein-antibody complex causes destruction of RBCs (innocent bystander; e.g., quinidine)
  58. 58. warm cold autoantibody immunoglobin G (IgG) chronic cold agglutinin disease: attacks red blood cells cold-activated immunoglobin M (IgM) and (RBCs); patients are complement (C3d) coat RBCs and trigger hemolysis; patients usually over age 50; sometimes resolves with usually over age 50; cold avoidance; rarely progresses to renal failure typically treated with corticosteroids andtherapies for underlying diseases Paroxysmal cold hemoglobinuria (PCH): rare disease induced most often by postviral Donath- Landsteiner autoantibody at cold temperatures in children; often acute and severe, though usually short- lived and self-limited; rarely progresses to renal failure, frank lymphoma, or death
  59. 59. CAUSES
  60. 60. Warm AIHA• Idiopathic: warm autoantibody IgG, its complement (C3d), or both, coat the red cell membrane and at 37°C induce phagocytosis• Secondary: warm antibodies produced by – lymphoproliferative disorders (e.g. non-Hodgkins lymphoma, chronic lymphocytic leukemia (CLL); – collagen vascular/autoimmune diseases (e.g. systemic lupus erythematosus (SLE) – HIV infection
  61. 61. Cold agglutinin disease• Idiopathic: the IgM autoantibody has an affinity for RBCs at cold temperatures (0ºC-18ºC); at warmer temperatures (37ºC, or 98.6ºF), when the two have no particular affinity, the IgM antibody can come off the RBC, but the remaining complement sticks. Hemolysis occurs as the liver and spleen remove complement- coated RBCs• Secondary: cold autoantibodies produced by – infections such as Epstein-Barr virus, Mycoplasma pneumoniae, and infectious mononucleosis – lymphoproliferative disorders, such as non-Hodgkins lymphoma and chronic lymphocytic leukemia (CLL)
  62. 62. Paroxysmal cold hemoglobinuria• Idiopathic: Donath-Landsteiner autoantibody• Secondary: viral infections (particularly in children and young adults), which produce the Donath-Landsteiner antibody
  63. 63. Predisposing factors• B-cell malignancy (produces hemolysis-inducing autoantibodies)• Family or personal history of autoimmune disease (produces hemolysis-inducing autoantibodies)• Viral infection in children (produces the Donath- Landsteiner autoantibody, which induces PCH)• Cold temperature (induces IgM activation in cold agglutinin disease)
  64. 64. SymptomsCommon for all AIHA:• Fatigue, dyspnea, malaise• Light-headedness or dizziness• Feeling hot and cold, or shivering (fever)• Abdominal/back pain• Occasionally abdominal fullness due to splenomegaly• Jaundice and dark urine
  65. 65. Specific for cold agglutinin disease:• Episodes of jaundice and dark urine• Acrocyanosis of hands, feet, earlobes, and/or tip of nose• Exposure to cold will precipitate symptomsSpecific for paroxysmal cold hemoglobinuria:• Paroxysms of hemoglobinuria on exposure to cold
  66. 66. SignsCommon for all AIHA:• Low hematocrit (<40% in males; <37% in females)• Pallor• Tachycardia, palpitations of the heart, and soft systolic murmurs• Jaundice, usually mild• Dark urine• Reticulocytosis• Palpable spleen/splenomegaly, especially if chronic (often secondary to B- cell malignancy)• Fever, secondary to underlying malignancy or infection• Weight loss, secondary to underlying malignancy• Secondary rash/petechiae/ecchymoses• Congestive heart failure (occasionally)
  67. 67. Specific for warm autoimmune hemolytic anemia:• Positive direct Coombs test previously reported in patient referred for transfusionSpecific for chronic cold agglutinin disease:• Skin findings include cool tips of the hands, feet, earlobes, and/or nose• Splenomegaly is common• Hemoglobinuria at cold temperatures in some patientsSpecific for paroxysmal cold hemoglobinuria:• Severe anemia• Hemoglobinuria• Hemoglobinemia• Renal failure
  68. 68. Investigation testsIn the differential diagnosis of AIHA, first determine whether there is anemia, then whether there is hemolysis.Order of tests• CBC with reticulocyte count• Peripheral blood smear• Urine dipstick for blood• Liver function tests for bilirubin• Liver function tests for serum lactate dehydrogenase (LDH)• Haptoglobin• Direct Coombs test• Cold agglutinin titer• Donath-Landsteiner autoantibody
  69. 69. Test FindingCBC with reticulocyte count hemoglobin and hematocrit vary in AIHA, but typically are low; the reticulocyte count, typically elevated in AIHA, is the hallmark indicator of red cell destructionLiver function tests bilirubin and LDH are breakdown products offor bilirubin and serum lactate hemoglobin; elevated levels provide additionaldehydrogenase (LDH) evidence of RBC destructionHaptoglobin binds in plasma with free hemoglobin when RBCs are destroyed; depressed haptoglobin provides additional evidence of hemolysisUrine dipstick for blood may be helpful to diagnose intravascular hemolysis by detecting hemoglobinuria If tests point to hemolytic anemia, then conduct further tests to determine whether the HA is caused by the hallmark autoantibodies of AIHA. Finally, if tests point to AIHA, prepare further tests to determine which specific autoantibody (IgG, IgM, or IgA) and/or complement is responsible for hemolysis (i.e. which specific AIHA is afflicting the patient).
  70. 70. Peripheral blood smear critical to the diagnosis of any anemia, it shows the number and morphology of different cell lines, and provides the visual evidence of hemolysis. In all warm AIHAs, macrophages transform disc shape of healthy RBCs to telltale spherocytes. Classically, reticulocytosis and nucleated red blood cells are also apparent. Examination of white blood cells and platelets provides clues to diagnosing hematologic or malignant disorders that sometimes coexist with AIHA. RBC aggregation on the smear suggests the diagnosis of cold AIHADirect Coombs test positive test indicates presence of autoantibodies (attached to RBCs); if positive, prepare an antibody eluate and examine the specificity for known RBC antigens Indirect Coombs test: positive test indicates the presence of autoantibodies (not attached to the RBCs) Thermal amplitude of the cold agglutinin indicates whether the antibody can bind RBC at physiologically relevant temperaturesDonath-Landsteiner If paroxysmal cold hemoglobinuria is suspected, confirmautoantibody diagnosis with test for hallmark Donath-Landsteiner autoantibody
  71. 71. Cold agglutinin titer useful if suspect cold agglutinin disease, in which titer usually is very high (from >1000 to >1:105). Titer does not predict severity of diseaseUrine hemosiderin staining the urine with Prussian blue or other iron stain can indicate whether there is hemosiderin present in the urine. If positive, this indicates possible hemolysis; however, other conditions of iron overload may also result in increased hemosiderin
  72. 72. Summary
  73. 73. Warm AIHA• Direct Coombs test is positive for immunoglobulin G (IgG), complement (C3d), or both• Spherocytes present on the peripheral blood smear• Phagocytized RBCs are typically sequestered in the spleen• Most patients quickly respond to corticosteroids, though the disorder is chronic and often relapsing• Refractory cases require prolonged immunosuppression or may undergo splenectomy; life- threatening cases may require transfusion
  74. 74. Chronic cold agglutinin disease• Positive direct Coombs test rarely detects cold-reactive IgM, but always detects C3d bound to RBC membrane• RBC aggregates seen on peripheral blood smear• Typically, cold agglutinin titer is very high• Idiopathic form of disease is frequently recurrent condition and often responds to cold avoidance; exacerbations are intermittent• Critical to explore diagnosis of B-cell lymphoma, which will determine therapy• Corticosteroids are usually not helpful• Splenectomy is rarely beneficial (unless splenic lymphoma) because RBCs destroyed primarily by C3d activation are sequestered in the liver, not spleen• In presence of B-cell neoplasm, chemotherapy or immunotherapy may help• Exposure to cold can prompt sudden drop in hematocrit and induce renal failure
  75. 75. Paroxysmal cold hemoglobinuria• Diagnosis generally relies on clinical presentation; routine tests do not pick up pathological Donath-Landsteiner autoantibody• Most often appears postviral in children and young adults• Symptoms may include fever, chills, abdominal distress, nausea, leg/back pain• Signs may include jaundice and hemoglobinuria• IgG detected in serum• Direct Coombs test is usually negative for pathological IgG and complement• Indirect Coombs test is negative• Diagnosis is confirmed with test for hallmark Donath-Landsteiner autoantibody• Often acute and severe, but usually short-lived and self-limited• Treatment includes: cold avoidance; supportive care; transfusions to alleviate symptoms; corticosteroids rarely useful• In rare cases can progress to renal failure
  76. 76. RED CELL ENZYME DISORDER G6PD deficiency
  77. 77. • G6PD – Rate-limiting enzyme in the pentose phosphate pathway – Essential for preventing oxidative damage to red cells• Def – susceptible to oxidant-induced haemolysis – X-linked, predominantly affect males
  78. 78. • Kids with G6PD deficiency typically do not show any symptoms of the disorder until their red blood cells are exposed to certain triggers.• Clinical features: – Sudden rise of body temperature and yellow coloring of skin and mucous membrane. – Dark yellow-orange urine. – Pallor, fatigue, general deterioration of physical conditions. – Heavy, fast breathing. – Weak, rapid pulse.• Once the trigger is removed or resolved, the symptoms of G6PD deficiency usually disappear fairly quickly, typically within a few weeks.
  79. 79. Investigations…• Bilirubin level (high)• Complete blood count, including red blood cell count• Hemoglobin – blood (low)• Haptoglobin level (low)• Methemoglobin reduction test• Reticulocyte count (high)• Blood film (concentrated and fragmented cells, ‘bite’ cells and ‘blister’ cells)
  80. 80. Management…• Medicines to treat an infection, if present• Stopping any drugs that are causing red blood cell destruction• Transfusions, in some cases