Acute Hemolysis.pptx

This is about emergency approach to a patient presenting with acute severe hemolysis. It mainly describes general approach and how to choose investigations appropriately. In depth discussion about the management of autoimmune haemolytic anaemia with warm antibody, cold antibody, all-immune antibody, drug induced, microangiopathic syndromes- TTP, HUS, DIC, Macrovascular hemolysis, sickle cell disease, thalassemia, G6PD deficiency, Hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria is included.

1. ED Approach to ACUTE hemolysis Dr KTD Priyadarshani Registrar in Emergency Medicine National Hospital- Kandy 2023/09/07

2. H emolytic anemia Definition Haemolytic anaemia is due to shortened survival of red blood cells (RBCs) in the circulation Normal RBC lifespan is about 120 days, therefore it is useful to think of haemolytic anaemia as representing RBC survival of <100 days It can be episodic or continuous

3. Classification Different classifications exists- Location- Intravascular (inside blood vessels) or extravascular ( spleen, liver) Mechanism- Immune or non-immune-mediated Defect- Extrinsic causes (immune, MAHA & infections) or intrinsic RBC abnormalities ( membrane, enzyme systems, Haemoglobin) Inheritance- Congenital/ inherited or acquired causes

4. Approach The approach to haemolytic anaemia involves: Confirm haemolysis Identify cause Specific management

5. History Clinical presentation and findings- symptoms of anaemia+ jaundice & dark urine Lifelong or family history? Ethnicity? Medication/drug precipitants  e.g. G6PD, AIHA? Acute versus chronic duration? Concomitant medical illnesses? Recent or current blood transfusion? Recent fever or travel? Recent bleeding, trauma or other systemic symptoms? History suggestive of connective tissue disorder, renal disease, malignancy or prosthetic valve, pregnancy

6. Examination Vital signs New onset of pallor and anaemia Jaundice Gallstones Splenomegaly +/- hepatomegaly Purpura, petechiae Murmur- prosthetic heart valve Stigmata of liver disease, renal disease

7. INVESTIGATIONS Confirm homolysis Increased absolute reticulocyte count LDH (elevation is more pronounced in intravascular haemolysis)- strikingly elevated in microangiopathic homolysis Total & Indirect Bilirubin (i.e. unconjugated). Total up to 4 mg/dL ( 68 µ mol/L) or more. Bilirubin higher than this may indicate some degree of hepatic dysfunction. Plasma free haemoglobin ( PFHb ) Decreased Haptoglobin (intravascular haemolysis)- A normal plasma protein that binds & clears free Hb released in to plasma, is decreased in HA. However, the haptoglobin level is influenced by many factors and in not always a reliable indicator of homolysis, particularly in liver disease. Urine Haemoglobin- when capacity of renal tubular cells to reabsorb Hb exceeds. Haemosiderin (useful in the diagnosis of prior intravascular haemolysis)- hemosiderin in shred renal tubular cells

8. Identify cause (history + peripheral blood film are the keys) FBC (thrombocytopenia? abnormal WCC?) Blood film spherocytes (AIHA, hereditary spherocytosis) helmet cells blister cells (oxidative damage in G6PD deficiency) schistocytes (TTP or DIC with thrombocytopenia) or heart valve homolysis (with thrombocytopenia) acanthocytes (liver disease) Heinz bodies (oxidative stress in G6PD deficiency, liver disease, thalassemia, splenectomy) Coagulation profile (distinguishes DIC, from HUS, HELLP, TTP etc) D-dimer, fibrinogen, INR, aPTT UEC (renal failure in MAHA, HUS and TTP)

9. Direct antigen test/ Direct Coombs test warm or cold IgG antiglutinin -mediated autoimmune haemolytic anaemia (AIHA) (can be negative if massive haemolysis) Coombs reagent- rabbit IgM antibody raised against human I gG or human complement. Patients’ anticoagulated, washed RBCs with anti immunoglobulin G and anti-C3d ( complement) antibodies to detect presence of immunoglobulin G and or complement on the R BC surface. Positive- either immunoglobulin G or complement on the RBC surface. i t is 90% specific for AIHA Presence of IgG &/or complement on a patient’s RBCs does not indicate the severity of the disease Indirect Coombs test Performed by mixing the patient’s serum with a panel of type O RBC. After incubation, the coomb’s reagent is added. Looks for the presence of autoantibodies in the patient’s serum- testing against a panel of RBCs bearing specific surface antigens

10. Special tests G6PD deficiency history of drug + at risk ethnic group Heinz body prep G6PD level once Hb normalises ADAMTS13 level (TTP) If recent or current blood transfusion send donor and recipient blood for repeat group, screen and cross-match Donath–Landsteiner test (PCH) Peripheral blood flow cytometry (PNH) free Hb (ECMO, LVAD to check for hemolysis )

11. Resuscitation S ymptomatic management Remove precipitants Blood product replacement (not platelets in TTP!) Supportive care Haematology consult Treat underlying cause and complications

12. A CQUIRED PATHOLOGIES Immune mediated Warm antibodies C old antibodies M ixed antibodies A lloimmune D rug induced M icroangiopathic syndromes TTP HUS DIC Macrovascular hemolysis

13. I mmune mediated acquired 3 main categories- autoimmune, alloimmune & drug induced A utoimmune- make Ab against their own RBCs T ested by direct Coombs test

14. AIHA- Warm antibody H emolysis is predominantly extravascular IgG A ntibody coated RBCs consumed mostly by splenic macropghages & liver- Kupffer cells P artial phagocytosis by splenic macrophage→ spherocyte → trapped in the red pulp of the spleen S pherocytosis found on peripheral smear correlates positively with severity of extravascular hemolysis W hen large amount of IgG are present in RBC, complement may be fixed. D irect complement lysis of cells is rare, but presence of C3b on surface of RBC allows Kupffer cells to participate in hemolysis

15. C ause I diopathic SLE O ther rheumatic disorders CLL Lymphomas C linical features T ypically produce rapid onset life threatening anemia S ymptomatic anemia with Heart failure Jaundice & heart failure I nvestigations FBC- severe anemia, HCT <10% ( Evans syndrome- 10% of patients coincident immune thrombocytopenia) R eticulocytosis B lood picture- spherocytes Coombs test-positive

16. Management S evere hemolysis- therapeutic plasma exchamge a a transient stabilizing measure B lood transfusion- transfuse allogenic RBCs without producing potentially harmful transfusion reaction A ssess for alloantibodies and autoantibodies H ematology and transfusion medicine consultation T ime consuming assessment- for emergency transfuse least incompatible units slowly and in smallest amounts necessary with close monitoring High dose corticosteroides- oral prednisolone 1-2 mg/kg/day in divided doses for 3-4 weeks followed by lower doses for 3-4 months I mprovement is expected in 80% to 85% of patients( both DAT positive or negative), but complete remission occurs in only approximately 30% of patients Monoclonal antibodies ( e.g rituximab) or immunosupressive agents ( e.g azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide) are used to decrease autoantibody production S plenectomy- removes main site of extravascular hemolysis in IgG mediated disease and a major site of general autoantibody production, clinical benefit in up to 60% of patients and potential for long term remission or a complete cure. S erious complication of splenectomy- overwhelming post splenectomy infection due to encapsulated bacteria

17. AIHA - Cold antibody Due to IgM autoantibody usually directed against the I/ i antigen on RBC At cooler parts of circulation ( fingers, nose, ears) IgM attach to RBC and trigger complement fixation on the RBC surface. Complement lysis of the RBC by membrane attach complex rarely occurs. When the RBC return to warmer temperature, the IgM antibody dissociates, leaving complemet on the cell. C3b recognosed by Kupffer cells & RBC sequestred and destructed in Liver. 2 major disorders C old agglutinin disease P aroxysmal cold hemoglobinuria 50% secondary cold antibody cases are associated with lymphoproliferative disorders, with underlying infection as the next uderlying casue

18. Cold agglutinin disease C ause I diopathic Waldernstrom macroglobulinemia L ymphoma CLL A cute post infectious cold agglutinin disease M ycoplasma pneumona, E coli. Listeria monocytogens, treponem apallidum. V iral infection – IMN, Measels. M umps, CMV, influenza, VZV, HIV Clinical features M ild anemia with reticulocytosis & rarely spherocytosis H emolysis 2-3 wks after the onset of illnes & resolves in 2-3 weeks I nvestigations B lood smear- at body temp- no agglutination/ at room temp- agglutinated RBC) D irect Coombs test- positive S erum cold agglutinin titer- semiquantitative Serum protein electrophoresis- M onoclonal IgM

19. M anagement Symptomatic management K eep patient warm S teroides U sually ineffective except when associated with lymphoproliferative disorder Considered in children with severe hemolytic anemia B ut benefit is uncertain bec au se the infection related disease is self limited. S plenectomy is not helpful P lasmaparesis as a temporising measure in lfe threatening cases If RBC transfusion is neces s ary, transfused blood should be infused at 37C using a blood warmer. Transfusions should be limited as they may worsen ongoing hemolysis because most cold antibodies act against the I/ i group antigens found on most donor RBCs. Donor complement in the transfused product also may exacerbate ongoing hemolysis R elapses can be treatet with high dose imminoglobulin, rituximab or cytotoxic agents such as cyclophosphamide, fludarabine or immunosupressive agents such as cyclosporin.

20. P aroxysmal cold hemoglobinuria C aused by biphasic hemolysin immunoglobulin G autoantibody ( Donath-Landsteiner DL Antibody) A ntibody binds to RBCs and fixes early complement components adhere and produce intravascular lysis of RBCs at warmer, physiologic temperatures B ursts of cold weather- induced intravascular hemolysis leads to bouts of dark urine or hemoglobinuria or high fever, chills, headache, abdominal cramps, nausea & vomiting, diarrhea & leg & back pain. A cute renal failure may revelop as a complication Ca uses P rimary- rare S econdary I n children After a preceding infection with adenovirus, influenza A, measels , mumps, EBV, CMV, Varicella, M Pneumoniae, H Influenzae or E Coli Managemnt Keep warm S teroids can be considered in children with severe HA I nfection related disease is self limited S econdary to syphilis- responds to effective antibiotic treatment S plenectomy is not helpful, P lasmaparesis as a temporising measure in lfe threatening cases RBC transfusion using a blood warmer should be limited to ases of severe anemia because most donor units are P antigen positive and may stimulate further production of antibodies.

21. M ixed antibody AIHA B oth warm and cold autoantibodies to RBC P resent as either primary or secondary disease C old- associated with lymphoproliferative and autoimmune diseases, particularly SLE T he course of illness is usually chronic with severe exacerbations U sually steroid responsive C an be treated with splenctomy and responds ot immmunosupressive therapy

22. A lloinmmune HA E xposure to allogenic RBCs with subsequent alloantibody formation C ommon cause- hemolytic disease of newborn RhD negative maternal immune system develops igG alloantibodies upon exposure to RhD positive fetal RBcs M aternal alloantibodies then cross the placentamledaing to fetal RBC destrusction A nemia range from mild to potentially fatal - IUD “hydrops fetalis” M anagemnt A dministration of anti-D immunoglobulin following fetomaternal hemorrhage event and soon after delivery E stablished hemolytic disease of newborn- intrauterine and intravscular fetal transfusion, plasma exchange or IV immunoglobulin therapy A dult- have a history of RBC transfusion which sensitizes patient to allogenic RBC antigens. A subsequent transfusion can rsult in immediate alloantibody production result in hemolytic transfusion reaction.

23. D rug induced HA R are 1in 1000,000 patients D rug coats RBC membrane & autoantibody is directed against the membrane- drug complex R esult either positive or negative direct test and can be difficult to distinguish from autoimmune hemolytic anemia R eview of current medications. & stop offending agents S ymptomatic treatment T ransfuse carefully screened RBCs S teroides in cases of severe HA

24. M icroangiopathic syndromes 2 classic syndromes- TTP and HUS P latelet aggregation in the mocrovascular circulation via mediation of von Willebrand factor. MAHA or Schistocyte forming hemolysis occurs fom fragmentation of RBCs during travel through these partially occluded arterioles and capillaries C auses TTP-HUS DIC Malignant disease V asculitis M a lignant hypertension Preeclampsia/HELLP Homograft rejection

25. T hrombotic thrombocytopenic purpura C lassic pentad CNS abnormalities R enal pathology F ever M icroangiopathic hemolytic anemia T hrombocytopenia U ntreated TTP carries a high mortality rate, but plasma exchange therapy can achieve remission of disease in >80% of patients Pathophysiology- deficiency in activity of ADAMTS-13 which is needed to cleave vWF. TTP is associated with ADAMTS-13 activity at levels <10% of normal

26. C auses- P regnancy HIV I nfluenza vaccine Acute pancreatitis D rugs- ciprofloxacin, ofloxacin, levofloxacin, quinine, sirolimus, risperidone, clopidogreal, lansoprazole, valcyclovir, mitimycin, infliximab, ticlopidine C linical features P latelet aggregation- thrombocytopenia M icroangiopathic hemolytic anemia E nd organ damge CNS- sizure, stroke, focal neurological deficits, coma R enal- AKI

27. Investigations Normal coagulation studies- distinguish from DIC Management P lamsa exchange therapy V ery effective- G oal to achieve a normal platelt count D aily plasmapharesis of 40 ml/kg or up yo 1-1.5 times a patient’s plasma volume is performed and then either weaned in frequency or stopped once normal platelet count is reahed for 2-3 consecutive days FFP If plasmapheresis cannot be performed immediately Infusion with factor VIII concentrate containing ADAMA-13 activity can be considered for patients with plasma allergy after specialist consultation and review

28. S evere TTP RBC transfusion A nticonvulsants A ntihypertensives H emodialysis A void platelet transfusion except in lifethreatening bleeding or ICH because acutely worsend thrombosis can lead to renal failure. A spirin- can exacerbate hemorrhgic complications in severe hthrombocytopenia. H eparin is not benefiical in TTP. C orticosteroides, rituximab and cyclosporine may be used in the treatment of autoimmune TTP Discontinue the inciting drug in all cases of drug associated TTP R elapse – new cae onset >30 days after completion of remission. I n 20%– 50% of cases T riggers are same as inciting original cases.

29. H emolytic uremic syndrome C onsists of microangiopathic hemolytic anemia, acute nephropathy or renal failure and thrombocytopenia C lassified as typical & atypical with prognosis favoring typical cases Typical HUS Atypical HUS (>90% of cases) occurs in children between 1-4 years P resenting in 1 weeks in to infectious diarrhea that is often bloody and without fever Causative organism- Shiga toxin producing E coli, with serotype O157:H7 5-10% of cases I n older children and adults C ausative organism- Streptococcus pneumoniae, EBV or noninfectious causes such as BM transplntation or administrstion of immunosupressant or chemotherapeutic agents

30. P athophysiology E coli O157:H7- possesses potent virulence factors that allow invasion of intestinal epithelial cells & subsequent transmural migration T he colonic inflammation produces hemorrhagic colitis S higs toxin is absorbed into systemic circulation, binds with greatest affinity to receptors found on the surface of glomerular & renaltubular epithelial cells & to a lesser extent to receptors lining cerebral, colonic & pancres epithelial cells M olecular mimcry may exist between human CD36 which is found on endothelial cells & platelets. T oxin mediated microvascular injury promotes platelet aggregation, thrombus formatin at the injury site, and shearing of RBCs. C linical features T ypically present 2-14 days after diarrhea develops – so may present with diarrhea illness phase or often without fever ARF 55-70%in typical HUS & 80% recover but atypical HUS permanent renal failure Or neurological damge M ortality 5-15% in typical 25% in atypical

31. Investigations N o bloody diarrhea stool for fecal leukocytes- occult inflammatory colitis S tool culture- for E Coli O157:H7 B lood diarrhea + S tool tesing for for Shiga toxin producing bacteria O ther Ix SE, RFT- detect nephropathy U rinalysis- RBC, RBC casts, protein M anagement Hydration RBC transfusion for significant anaemia Haemodialysis if ARF Do not use antimotility drugs for E Coli O157:H7 – increase risk of developing HUS, Antibiotics use is controversial- increase toxin expression from bacteria & risk of HUS Atypical HUS is treated with eculizumab- aggressive treatment significantly reduces incidence of permanent renal failure and lower the death rate.

32. M acrovascular hemolysis Occur in P rosthetic heart valve, intracardiac patch repair, aortofemoral bypass, coarctation of aorta, severe aortic valve disease,or ventricular assisst device or extracorporeal circulation- during CP bypass, plasma exchange or hemodialysis P rosthetic heart valves- Mechanical valves- turbulent blood flow with high shear stress across the valve C urrent models- due to perivalvular leak H emodialysis M echanical shear stress C hemical contaminant E xposure to dialysis membrane M anagement M ild- supplement iron & folate to promote healthy reticulocytosis Beta blocker in prosthetic heart valve- reduce HR & RBC shear stress P entoxifylline- reduce blood viscosity & improves RBC flexibility & deformability

33. Disseminated Intravascular Coagulation (DIC) S yndrome caused by systemic inflammation due to another undelying disease. C auses S epsis T rauma M alignancy P lacental abruption S evere liver disease P athophysiology- inflammatory cytokines that initiate the intrinsic (tissue factor) pathway of the coagulation. Simultaneously, endogenous fibrinolytic or anticoagulant systems cannot be maintained. This leads to excessive coagulation and consumption of platelets and clotting factors, which can subsequently lead to excessive bleeding as well at thrombosis

34. Investigations PT, APTT- prolonged D-dimer- elevated F ibrinogen- low B lood picture- schistocytes and RBC fragments M anagement Recognition of the disorder Proper resuscitation Platelets should be considered when the platelet count is < 50,000mm3 and/or significant bleeding is present. RBCs should be provided if there is active bleeding present and or if the patient is hemodynamically unstable Coagulation factor replacement with fresh frozen plasma (FFP) should also be given when active bleeding exists If massive bleeding is present or fibrinogen is < 150, fibrinogen should be replaced via cryoprecipitate Anti-fibrinolytic treatment, such as tranexamic acid is recommended only for the active or massive bleeding Treatment of the underlying disorder and when indicted Treatment focused on reversing the coagulopathy

35. H EREDITARY PATHOLOGIES R esult fro defects in Hb production, abnormalities in RBC metabolism or changes with in RBC membrane structure. A bnormal Hb structure S ickle cell disease D isorders of abnormal Hb production thalassemia

36. S i ckle cell disease Autosomal recessive disorder A single DNA base change leads to amino acid substitution of valine for glutamate in the 6 th position on the beta globin chain Haemoglobin S is unstable and polymerises in the setting of various stressors, including hypoxemia & acidosis leading to formation of sickled RBCs. I nitiating event may not be identifiable, but stressors such as infection, cold, dehydration and altitude.

37. Chronic hemolytic state due to shape of the RBC. B aseline Hb is 6-9 g/dL, retic count 5-15% Blood picture sickled cells 5-50% of RBC Hyposplenism Howell-Jolly bodies Target cells W ith infection, hemolytic process may worsen & Hb may drop from previous baseline I t is uncommon for the hemolysis to be so severe as to require transfusion

38. Thalassemia D efective synthesis of globin chains, resulting in an inability to produce a normal adult Hb H allmark is- microcytic, hypochromic, hemolytic anemia C ategorised depending on the globin chain affected or the abnormal hemoglobin produced. A lpha thalassemia B eta thalassemia

39. Thalassemia type Clinical features 𝜶 𝒕𝒉𝒂𝒍𝒂𝒔𝒔𝒆𝒎𝒊𝒂 𝒄𝒂𝒓𝒓𝒊𝒆𝒓 & 𝒕𝒓𝒂𝒊𝒕 N o clinical symptoms or signs D etected by microcytic RBC & a boderline to slightly low Hb 𝛼 𝑇ℎ𝑎𝑙𝑎𝑠𝑠𝑒𝑚𝑖𝑎 ( 𝐻𝑏 𝐻 𝑑𝑖𝑠𝑒𝑎𝑠𝑒) Ineffective erythropoiesis & increased homolysis Marked phenotype variation in the clinical picture- IUD to mild anaemia in adulthood Chronic hypochromic microcytic anaemia & homolysis, which worsens during oxidant stress P rotective for malaria S upportive & include avoidence of unnecessary iron therapy 𝛃 thalassemia minor ( trait) H eterozygous fro globin mutation O nly mild microcytic anemia S plenomegaly +/- B lood smear- microcytosis & hypochromia, basophilic stipplins H b A2 – 4-6 % confirms the diagnosis N o clinical manifestations 𝛃 thalassemia intermedia G enetic combination of b gene mutations P rduce microcytic moderate anemis ( Hb >7 g/dL), splenomegaly, intense bone marow hyperplasia HbF levels are elevated. C linical symptoms- milder & delayed compared to thal major V ariable tansfusion requirement

40. 𝛃thalassemia major ( cooley’s anemia) B oth 𝛃 globin chains are defective & production of 𝛃 globin chains is severly impaired N ewborn infants- usually well because of Hb F is predominant S ymptoms emerge during second 6 months of life RBC- low MCV with microcytic & hypochromic cells. V ariation in size & shape of RBCs will be notable ( increased RBC distribution width), presence of neucleated cells HbF remain elevated >90% of under transfused individuals A ffected children develop hepatosplenomegaly, jaundice and expansion of the erythroid marrow, causing bone changes & osteoporosis & posses increased susceptibility to infection. T he anemia is severe – requires regular, lifelong blood transfusions I ron overload- hemochromatosis in cardiac, hepatic and endocrine dysfunction N eed chelation, with parenteral ( desferrioxamine) or oral ( deferiprone and defarasirox) agents

41. G -6-PD Deficiency M ost common enzymopthy of RBC in humans affecting >400 million people worldwide >400 variants X linked inherited disorder- primarily affect males, females must have 2 defective genes to be affected. B ut because expression of this gene is variable, women with one abnormal gene may still show some symptoms M ost adults are usually asymptomatic- but may have intermittent hemolytic anemia & few have chronic hemolysis G6PD deficient RBC is susceptible to oxidative stress and precicpitated hemoglobin is recognized by the presence of heinz bodies on the peripheral blood smear. T he affected RBC are removed from the circulation by the spleen- extravascular hemolysis

42. Diagnosis E stablished by the demosntration of decreased enzyme activity through quantitative assay. ( P erform weeks after hemolysis resolves) B lood film- evidence of oxidative hemolysis B ite cells B lister cells H eniz bodies- precipitated membrane Hb aggregates A cute symptoms- FBC, reticulocyte count ( to evaluate level of anemia & BM function). Hb rarely falls below 8 g/dL. serum bilirubn levels, serum aminotrnasferases ( to exclude other causes of jaundice) U rinalysis ( hemoglobinuria) L actate dehydrogenase ( elevated in hemolysis and a marker of hemolytic severity)

43. T reatment D etermined by patient’s overall clinical condition & removal of offending agent, if present. I f the illness is severe blood transfusion with RBCs F luids- prevent renal injury K nown G6PD – ag g ressive treatment for infections and avoid oxidative drugs Drugs with solid evidence to cuase acute hemolysis in patients with G6PD- dapsone, phenazopyridine, nitrofurantoin, primaquine, rasburicase, pegloticase, mehtulthioninum chloride ( methylene blue) and tolotnium chloride ( toliuidine blue) Even with continuous use of the offending medication, the hemolytic episode is self limited because older RBC with low enzyme activity are removed and replaced with a population of young RBC with adequate functional levels of G6PD.

44. H ereditary Spherocytosis D ue to eryhthrocyte membrane defect I nheritance autosomal dominant pattern + less common autosomal recessive variant exists C linicl features M ild disease- 20% autosomal dominant inheritance N ormal Hb, little or no splenomegaly, but susceptible to hemolytic or aplastic episodes triggered by infection M oderate disease- 75% autosomal dominant inheritance M ild to modearate anemia, modest splenomegaly, periodic episodes of hemolysis with jaundice and and an increased incidence of pigmented gallstones. S evre- 5% autosomal recessive inheitance S ignificant hemolytic anemia requiring blood transfusion, chronic jaundice and an enlarged spleen. M ain complicatins- aplastic or megaloblastic crisies, hemolytic crises. C holecystitis or cholelithiasis & neonatal hemolysis with jaundice. N eonatal jaundice during 1st week of life in 30-50%

45. D iagnosis Peripheral blood smear- spherocytes with normal to low MCV and increased MCHC >36% D iagnosis= clinical+ examination+ family history+ RBC indices & morphology T reatment S evere anrmia- RBC transfusions, splenectomy

46. P aroxysmal nocturanal hemoglobinuria R are acquired clonal hematopoetic stem cell disorder- result in abnormal sensitivity of the red cell membrane to lysis by complement and therefore hemolyis. C linical features E pisodic hemoglobinuria- reddish brown urine often noticed in the first morning urine due to fall in blood pH while sleeping ( hypoventilation) P rone to thrombosis- mesenteric, hepatic, Sagital vein, skin vessels ( painful nodeuls). M ay associate with AML, idiopathic aplastic anemia Investigations Urine hemosiderin- episodic hemolysis Serum LDH- quite elevated B est screening- flow cytometry of RBC & WBC to demonstrate deficiency of CD55 & CD 59

47. T reatment M ild disease- not requiring intervention S evere disease A ssociated myelodysplasia or previous aplastic anemia- allogenic hematopoetic stem cell transplantation S evere hemolysis- usually require BT or thrombosis or both- Eculizumab H umanised monoclonal antibody against complement protein C5 given every 2 weeks Binding Eculizumab to C5 prevent clevage so membrane attack complex cannot assesmble I t improves quality of life & reduces hemolysis, transfusion requirements, fatigue & thrombosis risk Corticosteroides- decrease hemolysis

48. Take home message A R ule of thumb! In the critically ill, always consider: ABO incompatibility due to recent transfusion Clostridium  sepsis and malaria Medications causing an autoimmune response Extra-corporeal circuits Life in the fast lane - Hemolytic anemia

49. R eferences Tintinali 9th Edition Life in the fast lane https://www.emdocs.net/hemolytic-anemias-rare-important-diagnosis-emergency-department/ Essential Hematology- 6th edition CMDT- 2020