Acquired Hemolytic Anemias

Paroxysmal Nocturnal Hemoglobinuria

mutation(s) in the hematopoietic stem cell → membrane defect → loos of anchoring proteins → blood cells are sensitive to complement → hemolysis.infection/thrombi

PNH I

reacts normally with complement

PNH II

decreased DAF (decay Accelerating Factor or CD55)
normally inactivates C3 convertase
3-5x more sensitive to complement

PNH III

decreased DAF
decreased MIRL - membrane inhibitor reactive lysis/CD59/Protectin
normally prevents C9 from binding cell
15-25x more sensitive to complement

PNH clinical features

middle age
hemoglobinuria (first morning) → hemosiderinuria
abdominal pain, headache, backaches
venous thrombosis, infections, aplastic anemia

PNH Laboratory findings

decreased RBC, Hb, Hct (Normo/normo with Hb 6 g/dL)
Pancytopenia - increased retics, poly, NRBC
Schistocytes
Hemoglobinuria → hemosiderinuria → IDA
increased plasma Hb, decreased haptoglobin, increased bili, (-DAT)

Ham’s test

PNH confirmatory Laboratory findings
decreased pH → activates complement → RBC lysis

Sucrose hemolysis test

PNH confirmatory Laboratory findings
decreased ionic strength → activates complement → RBC lysis

Flow cytometry

PNH confirmatory Laboratory findings
absence of CD55, 59, 16 (major)
CD14, 24, 48, 52, 58, 66, 67 (minor)

PNH treatment

Fe2+ and/or transfusion for anemia
antibiotics for infection
anticoagulants for thrombosis
steroids for hemolytic events (controls complement)
Eculizimab (anti-C5)
erythropoietin

PNH prognosis

average 10 year survival
can survive for 20-43 years
can spontaneously remit or develop AML

Immune Mediated Hemolytic Anemia

shortened RBC survival from anti-RBC ab

Alloimmune

Ab against foreign RBCs

Autoimmune

Ab against self RBCs

Drug-induced

drug causes Ab against self

Hemolytic disease of the newborn

Dad’s Ag on baby → mom’s immune system reacts → Ab made → crosses placenta to react with 2nd child

Warm AIHA etiology

RES neoplasms
Collagen Vascular diseases
Lupus, RA, scleroderma, polyarteritis nodosa, anklosing spondylitis, dermatomyositis, psoriatic arthritis
infection, immunologic, GI, tumors, idiopathic

Warm AIHA Clinical features

weakness, pallor, dizziness, dyspnea
hemolysis, fever, anemia, jaundice

WAIHA Ab sensitization

+DAT, spherocytes, schistocytes (increased osmotic fragility)

WAIHA treatment

underlying disease, steroids, splenectomy, ImmSup

Normal cold antibodies

Anti-I IgM. 

Cold Agglutinin Syndrome

idiopathic IgM, Anti-I → complement → hemolysis
>50yo in winter → ling term condition
cyanosis, weakness, pallor, weight loss
BM: increased poly, retics, NRBC, + DAT, spherocytes

Secondary Cold AIHA

mycoplasma or IM → Anti-I → 2-3 weeks → increased hemolysis
BM: increased poly, retics, NRBC, + DAT, spherocytes
Keep warm (cold agglutinin test → pt serum + O RBCs)

PCH Etiology

Children → viral disorder → anti-P (P1-79% of RBCs) → sensitize RBCs in cold → fix complement → hemolysis in warm
Sudden symptoms → fever, chills, cramps, back pain, hemoglobinemia, hemoglobinuria → resolves after infection but protect from cold  

PCH lab findings

Anemia, increased bilirubin
polychromasia, NRBCs, increased retics (BM response)
spherocytes → osmotic fragility

Donath-Landsteiner Test

PCH lab test
collect 2 tubes from patient
incubate 1st tube at 37C → no hemolysis (cold IgM Ab does not bind nor fix complement
incubate 2nd tube at 4C for 30 minutes (Ab binds) → 37C for 30 minutes → hemolysis

Immune complex mechanism

mechanism of Drug-induced hemolytic anemia
drug → anti-drug → complex → RBC → complement → lysis
+DAT until drug is discontinued

Drug absorption Mechanism

mechanism of Drug-induced hemolytic anemia
penicillin → RBC → anti-drug → complement → lysis
+DAT until drug is discontinued

Membrane Modification Mechanism

mechanism of Drug-induced hemolytic anemia
cephalosporins (antiboitic) → alter RBC membrane → plasma proteins absorb → anti-complex → usually no hemolysis
+DAt until drug is discontinued and can be chronic

Mehtyldopa Induced Mechanism

mechanism of Drug-induced hemolytic anemia
Aldomet (decreased BP) → anti-RBC → complement → lysis
+DAT until drug is discontinued and can be chronic

remove/change drug

treatment for Drug-induced hemolytic anemia

Arsenic

causes Hemolytic Anemia
industrial inhalation or homicide → binds RBCs → hemolysis → nausea, vomiting, abdominal pain → anemia, jaundice, Hburia → chelation → exchange TX

Copper

causes Hemolytic Anemia
affects RBC membrane and glycolytic pathway

osmotic damage

causes Hemolytic Anemia
water injection IV, drowining → RBC swelling → Burst

Venoms

causes Hemolytic Anemia
bees, wasps, spiders, scorpions, snakes

burns

causes Hemolytic Anemia
RBCs are damaged by heat → microspherocytes → schistocytes → Hbemia → Hburia

Macroangiopathic Hemolytic

Hemolytic Anemia
tissue/cell
Prosthesis
Heart valves
Stents

Microangiopathic Hemolytic

Hemolytic Anemia
molecular
Excessive clotting → shear RBCs → hemolysis

Thrombotic Thrombocytopenic Purpura

Microangiopathic Hemolytic
ADAMTS-13 mutation → decreased cleavage of vWF
platelet activation → clumping → decreased platelet count

DIC

Microangiopathic Hemolytic
pre-ecclampsia (Others) → activation of coagulation → thrombi → RBC fragments → hemolysis → decreased platelets

Hemolytic Uremic Syndrome

Microangiopathic Hemolytic
children → glomerular damage → uremia → platelet aggregation → clots → RBC shearing → hemolysis
Nausea, vomiting → hypertension → renal failure (decreased EPO)
schistocytes, thrombocytopenia, increased retics, NRBC, WBC
supportive therapy, anti-hypertensives, dialysis, blood Tx

Metastatic Cancer

Microangiopathic Hemolytic
unknown mechanism