Hemolytic anemia Flashcards
Hemolytic anemia definition
increased red cell destruction resulting in a reduced RBC Lifespan.
Inhertied and acquired
Hemolysis can be intravascular vs extravascular
Hereditary Spherocytosis
75% autosomal dominant, 25% sporadic
Defect of RBC cytoskeleton-membrane tethering protein (typically involves ANKYRIN SPECTRIN Band 3 or BAND 4.2)
RBC membrane bleb forms, leading to non deformability and destruction in the spleen
Blood smear has SPHEROCYTES, increased RDW, increased MCHC (concentration of hemoglobin, as membrane is lost, hgb concentration goes up), Osmotic fragility
Splenomegaly, jaundice (unconjugated bilirubin) , increased risk for gallstone. Aplastic crisis (parvo B19 attacks the erythrocyte precursors)
Treatment- splenectomy (spherocytes persists dont get broken up, also howel jolly bodies still present bc splenic macrophages are gone)
Sickle cell anemia
Autosomal recessive mutation of the B chian of hemoglobin, a single amino acid change replaces normal glutamic acid (hydrophillic) with valine (hydrophobic). CALLED CHRM 11
High af am inident, SCA is present when 2 abnormal B genes are present, results in >90% Hb S in RBCs
Increased risk for sickling when DEOXYGENATION, HYPOXIA, DEHYDRATION, PROLONGED TRANSIT time
Cause microvasculature occlusions and RBC lysis. Cells continue to sickle and sickle constantly causing membrane stiffness–> extravascular splenectomy hemolysis (ANEMIA, JAUNDICE, HYPERBILIRUBINEMIA, increased risk of gall bladder stones). SLightly causes intravascular hemolysis (RBC membrane damages–> dehydration–> lysis–> release of free hemoglobin–> free hgb gets bound to haptoglobin–> low haptoglobin. Dehydrated cells also get target cells
Massive erythroid hyperplasia (crew cut skull, chipmunk facies, hepatomegaly) aplastic crises due to parvovirus B19,
HGB HPLC (chromatography) identifies HbS
Pain crisis, acute chest, stroke, Encapsulated bacterial infections due to auto splenectomy, Salmonella osteomyelitis
Thalessemia
HGB is globin and heme. Thalessemia is a reduced globin production of (beta- betathalessemia) or alpha (alpah thalessemia)
Low globin–> low hemoglobin–> microcytic anemia
HbF (2 a + 2 gamma), Hb A (2a + 2B), HbA2 (2a + 2 delta)
Alpha thalessemia
Gene deletion, normally there are 4 alpha genes on chromosome 16
One gene is deleted- asymptomatic,
2 gene deleted mild anemia with increased RBC,
3 genes deleted severe anemia- Beta chains form tetramers (HbH) that damage RBCs
4 gene deletions- lethal, hydrops fetalis, y chains form tetramers (hb barts) damage RBC
Beta thalessemia
gene mutations, point mutations in promoter or splicing sites, seen in individuals of african and meditteranean
2 B on chromosome 11, mutation is either absent (B0) or lowered B (B+)
Beta thal minor- usually asymptomatic, microcytic hypochromic RBCs, target cells, elevated Hb A2,
beta thal major- very severe, presents a few months after birth, unpaired alpha chains percipitate and damage RBC,ineffective erythropoiesis, expansion of erythropoiesis in random bones, chronic transfusions are required and lead to hemochromatosis (increased lead)
G6PDH
X linked recessive disorder
Reduced half life of G6PD (generally a RBC has a half life of G6PDH that is long enough to sustain RBC for 120 days)
We need G6PDH bc the RBC is constatntly in a oxygen rich area–> oxidative stress specificially from H2O2, GSH can take up the Oxygen–> GS GS, with NADPH convertign GSGS back to GSH. NADPH is made via G6PDH
Africant variant slighly shortened G6PD, medditernean extrememly short
Oxident stressors cause HEINZ BODIES, damage the cells and intravascular, and removed by the spleen macrophages leading to Bite cells
Males>Females,
Paroxysmal nocturnal hemoglobinuria
Stem cell with dificiency in GPI linked proteins on RBCs and WBCs) including anticomplement CD55 (DAF), CD59
RBCs under go intravascular hemolysis episodically especially at night when there is an increased acid, increasing compleemnt.
RBCs WEBs and PLatelets are lysed–> hgb release, also leading to thrombotic factors are released. can also get hemosiderinuria
Sucrose testing, FLOW CYTOMETRY CD55
Main cause of death is thrombotic events
Warm autoimmune hemolytic anemia
RBC Auto antibodies (IgG)- that rect at 37 C causing intravascular coating of RBCs and removal in the spleen
Ig eGypt
Spherocytes and positive DAT
Splenomegaly
Assocaited with B-cell lymphoproliferative disorders
Cold autoimmune hemolytic anemia
RBC autoantibodies IgM that react at <30 C and may lead to extravascular hemolysis C3b opsonization in the spleen or liver
Minesota
Smear for spherocytes DAT positive
Raynauds mycoplama infection and EBV infections (anti-i)
Microangiopathic hemolytic anemia
Traumatic sheering and subsequent lysis of RBCs due to vascular obstruction by microthrombi
Schistocytes
ADAMTS 13 for TTP coagulation tests for DIC
metastatic carcinoma, malignant HTN, HELLP syndrome
Physical trauma to RBC
traumatic RBC injury due to turbulent blood flow/increased shear stress
Smear review for schistocytes
Mechanical cardiac valves
Malaria babesia
intacellular parasites infect RBC and cause lysis as they propagate
Parasites on microspoe
PCR assays
cyclic fever, cerebral malaria (falciparum)
Blackwater fever
acquired spherocytes
autoimmune, thermal injury, oxidant fragmentation, post transfusion
WARM VS COLD
postive DATs are seen in
immune mediated processes
