Autoimmune hemolytic anemias.docx

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Biochem. and Medical Genetics
BGEN 3020
Jason Leboe- Mcgowan

Autoimmune hemolytic anemias Warm reacting antibodies are IgG and cold reacting is IgM MC autoimmune hemolytic anemia = warm; MCC of it = Lupus When you have autoimmune dz in your family, you have certain HLA types that predispose you to that autoimmune dz. Therefore, you should not be surprised if you have one autoimmune dz you’re likely to have another. So, pts with lupus commonly also have autoimmune hemolytic anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and autoimmune lymphopenia. For example: the MCC of hypothyroidism = hashimoto’s thyroiditis; these pts commonly have other autoimmune dz’s – ie pernicious anemia, vitiligo, autoimmune destruction of melanocytes). So, if you have one autoimmune dz, you are likely to have others (ie if you have a hemolytic prob, it is prob autoimmune related). This is b/c of the HLA relationship. Therefore, if you have a family that has an autoimmune dz, what would be the single best screening test to use? HLA (ie if they have the HLA type specific for lupus – there are specific HLA’s for diff dz’s). Therefore, HLA is the best way to see if pt is predisposed to something. MCC autoimmune anemia = Lupus; it has IgG and C3b on the surface of the RBC, so it will be removed by the macrophage. This is an extravascular hemolytic anemia. How do we know that there are IgG or C3b Ab’s on the surface? Direct Coomb’s test: detect DIRECTLY the presence of IgG and/or C3b on the surface of RBC’s. Indirect coombs is what the women get, when they are pregnant and they do an Ab screen on you (looking for any kind of Ab); so, when you look for Ab in the serum (NOT on RBC, on SERUM), this is an indirect Coombs. Therefore, another name for the indirect Coombs = Ab screen; with direct coombs, we are detecting IgG and/or C3b on the SURFACE of RBC’s. you cannot do direct coomb’s on platelets or neutrophils, but only RBC’s. So, the test of choice if you suspect an autoimmune hemolytic anemia is Coomb’s test. Drug induced autoimmune hemolytic anemias: nd There are 3 types of drug induced hemolytic anemia (2 MCC autoimmune hemolytic anemia = drug induced; MCC = lupus) PCN – mechanism: the bpo group of PCN attaches to RBC (lil piece of PCN is attached on RBC membrane). This is bad if an IgG Ab develops against it b/c if it does, than the IgG attaches to the bpo group, goes to the spleen and is removed extravascularly; this is an ie of type II HPY Example: pt on PCN develops a rash – what type of HPY? Type I. Example: Pt on PCN develops a hemolytic anemia – what type of HPY? Type II Methyldopa – aka aldomet. Use: anti-HTN for pregnant woman (other anti-HTN used in pregnancy = hydralazine). Methyldopa and hydralazine have complications – methyldopa can cause a hemolytic anemia; hydralazine can lead to drug-induced lupus (2 tond procainamide for drug induced lupus). Methyldopa works differently from PCN: methyldopa messes with Rh Ag on surface of RBC and alters them. They are altered so much that IgG Ab’s are made against the Rh Ag (our OWN Rh Ag). So, the drug is not sitting on the membrane, it just causes formation of IgG Ab’s and they attach to RBC to have macrophage kill it – what type of HPY is this? Type II. Therefore, methyldopa and PCN are type II for hemolytic anemia. Quinidine: this is the ‘innocent bystander’ b/c immune complexes are formed. Quinidine acts as the hapten, and the IgM Ab attaches; so, the drug and IgM are attached together, circulating in the bloodstream. This is a different HPY – type III, and will die a different way, b/c this is IgM. When IgM sees the immune complex, it will sit it, and activate the classical pathway 1-9, leading to intravascular hemolysis, and haptoglobin will be decreased, and in the urine, Hb will be present. Microangiopathic hemolytic anemia RBC’s all fragmented – schistocytes (schisto – means split). MCC chronic intravascular hemolysis = aortic stenosis, in this dz, the cells hit something; therefore have intravascular hemolysis, Hb in the urine and haptoglobin is down. This is a chronic intravascular hemolysis, and you will be losing a lot of Hb in the urine; what does Hb have attached to it? Fe; so what is another potential anemia you can get from these pts? Fe def anemia. Example: will describe aortic stenosis (systolic ejection nd murmur, 2 ICS, radiates to the carotids, S4, increased on expiration, prominent PMI), and they have the following CBC findings: low MCV, and ‘fragmented’ RBC’s (schistocytes) – this is a microangiopathic hemolytic anemia related to aortic stenosis. Other causes of schistocytes: DIC (lil fibrin strands split RBCs right apart b/c RBC is very fragile); thrombotic thrombocytopenic purpura, HUS – see schistocytes. When you have platelet plugs everywhere in the body, the RBCs are banging into these things causing schistocytes and microangiopathic hemolytic anemia. Example: runner’s anemia, esp. long distance you smash RBC’s as you hit the pavement; very commonly, you go pee and see Hb in it; to prevent, use bathroom b4. Another cause of hemolytic anemia: malaria – falciparum b/c you have multiple ring forms (gametocyte (comma shaped and ringed form). It produces a hemolytic anemia, which correlates with the fever. The fever occurs when the cells rupture (the hemolytic anemia). Intrinsic vs. Extrinsic Hemolytic anemia: 1. Intrinsic – something wrong with RBC, causing it to hemolyze: such as no spectrin, or not decay accelerating factor to neutralize complement, no G6PD enzyme in pentose phosphate shunt, or abnormal Hb (ie HbS). Therefore, something wrong inside the Hb molecule, causing it to hemolyze. 2. Extrinsic – nothing wrong with the RBC, just at the wrong place at the wrong time; ie it just happened to smash into the calcified valve (nothing was wrong with it, until it hit the valve). Then it will be dreading going to the cords of bilroth with destroy it b/c it has been marked with IgG and C3b for phagocytosis. Something intrinsically wrong with the RBC causing it to hemolyze but there’s nothing wrong with the BM (but something intrinsically wrong with the RBC), and the corrective ret ct is greater than 3%. MAD – MC intrinsic probs Membrane defect (spherocytosis, paroxysmal nocturnal hemoglobinuria), Abnormal Hb (SC trait Dz), Deficiency of enzyme (G6PD def). Membrane Defects: (a) Spherocytosis: do no see a central area of pallor therefore must be a spherocyte and must be removed extravascularly. Clinically manifest with jaundice from unconjugated bilirubin. Spectrin defect and AD dz; splenomegaly always seen over a period of time. Gallbladder (GB) dz is common b/c there is a lot more unconjugated bilirubin presented to the liver and more conjugation is occurring and more bilirubin is in the bile than usual. So, whenever you supersaturate anything that is a liquid, you run the risk of forming a stone; if you supersaturate urine with Ca, you run the risk of getting a Ca stone; if you supersaturate bile with cholesterol, you will get a cholesterol stone; if you supersaturate with bilirubin, you will get a Ca-bilirubinate stone. Therefore, pts have GB dz related to gallstone dz and then do a CBC with normocytic anemia and a corrected ret ct that is elevated, and see congenital spherocytosis. What’s the diagnostic test? Osmotic fragility – they put these RBC’s wall to wall in different tonicities of saline, and the RBC’s will pop (therefore have an increased osmotic fragility). Rx: splenectomy (need to remove organ that is removing them – they will still be spherocytes and will not be able to form a biconcave disk). (b) Paroxysmal Nocturnal Hemoglobinuria = defect in decay accelerating factor. So when we sleep, we have a mild resp acidosis b/c we breathe slowly (if you have obstructive sleep apnea, the acidosis is worse). When you have acidosis that predisposes the complement that’s sitting on ALL cells circulating in pe
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