immune mediated hemolysis

microangiopathic hemolytic anemia (MAHA)

• cells fragmented pasing through fibrin clots in small vessels

• results in intravascular hemolysis

• TTP, HUS, DIC, HELLP, sepsis, disseminated cancer

• non-immune acquired

MAHA TTP

thrombotic thrombocytopenic purpura

• hemostasic disorder

• caused by disseminated thrombotic occlusions of microcircluation

• microthrombi = platelets, fibrin and vWf

• deficiency in ADAMTS13 or ultra large vWf which helps facilitate rapid platelet binding

• associated with infectious diseases, immune disorders, pregnancy

• damages vascular endothelium

• non-immune acquired

MAHA TTP findings

Pentad symptoms

• hemolytic anemia

• thrombocytopenia

• neurologic dysfunction

• fever

• renal failure

most common in ages 30 to 40

treatment for MAHA TTP

units of FFP

plasmapheresis

plasma exchange

antiplatelet drugs

MAHA TTP lab results

• less than 10g/dL hemoglobin

• schistocytes, helmet, traingular scells, microspherocytes, polychromasia

• very low platelet count

• left shift with WBCs

• renal dysfunction hematuria and proteinuria

MAHA HUS

hemolytic uremic syndrome

triad symptoms

• severe anemia

• acute renal failure

• thrombocytopenia

occurs more in kids 6 months to 4 years after a febrile illness

MAHA HUS pathophysiology

• enterotoxin from anerobes or step pneumo

• causes intravascular platelet actiation

• injures vascular endothelium in kidneys

• treat by managing renal failure with dialysis

MAHA HUS lab results

• anemia with RBC fragmentation (Schistocytes and increased retics)

• thrombocytopenia

• proteinuria

• RBCS and RBC casts in urine

• abnormal vW molecules

• possible abnormal hemostasis

MAHA HELLP

hemolysis, elevated liver enzymes, low platelets

• pregnancy-specific MAHA variant

• linked to preeclampsia

• risks factors: first pregnancy, multiple pregnancy, advanced maternal age

• symptoms: RUQ pain, headache, nausea, hypertension, edema

MAHA HELLP lab results

• increased LDH

• increased bilirubin

• schistocytes

• increased AST

• increased platelets

• diganose with clinical lab have to rule out TTP and HUS

MAHA DIC

• sepsis, trauma, malignancy, obstestric event

• any age (critically ill)

• multiorgan failure

• prolonged PT and APTT

• low fibrinogen

• increased D-dimer and FDPs

other extrinsic HA

infectious organisms:

• malaria (ID on smear)

• babesia (ID on smear)

• clostridia

venoms: spiders and snakes

drugs, chemicals: water, oxidants, lead

severe burns

• 2nd or 3rd degree burns over more than 40% of the body

• inhalation injury

• can lead to DIC

• see microspherocytes

• budding nRBCs

• schistocytes

• toxic changes and left shift

• decreased platelets

anemia of hemorrhage

• involved rapid and significant loss of blood cells and plasma

• dizziness

• tachycardia

• shallow, irregular pulse

• profuse sweating

• cyanosis

• unconsciousness

• treat with fluids for hypovolemia and pRBCs for hypoxia

immune mediated hemolysis pathway

1. IgG tags red cells for phagocytosis (spleen)

2. IgM activates complement, less efficient in tagging

3. complement can mark cells or directly lyse them

4. C3b is for phagocytosis

5. C9 leads to intravascular hemolysis

IHA classifications

1. autoimmune hemolytic anemia (AIHA)

2. alloimmune hemolytic anemia

3. drug induced hemolytic anemia

autoimmune hemolytic anemia (AIHA)

• antibodies against RBC antigens which leads to hemolysis

• severity varies

• can be warm autoimmune

• can also be cold auotimmune (PCH)

• mixed type

warm autoimmune hemolytic anemia

• most common type

• usually IgG cuz they react at body temp

• primary is idiopathic

• secondary is associated with CLL, lymphoma or Evans syndrome or certain infections/medications

• usually extravascular hemolysis

AIHA cold

usually Igm since reacting at colder temps

• primary is idiopathic (chronic in older adults, specifcally auto-anti-I)

• seoncdary is associated with IM (anti-i specifcity)

• mycoplasma pneumoniae

AIHA cold agglutinin

• RBC clumps on smear

• differ from rouleaux

• blood has tob e warmed before running a CBC

AIHA lab results

• positive DAT

• anemia

• polychromasia

• spherocytes

• nRBCs

• increased bilirubin

• increased LD

• decreased haptoglobin

hemolytic transfusion reactions

• alloimmune

• usually human error is cause

• blood given to misidentified patient, usually ABO incompatibility

• can be immediate (IgM and intravascular)

• can be delayed (IgG, extravascular)

HDFN

• erythroblastosis fetalis

• severe hemolytic anemia

• jaundice

• intravascular hemolysis

• extramedullary hematopoiesis

• can cause kernicterus

• less comon now due to RhIG

• usually due to Rh or ABO

HDFN cause

• infant has RBC antigen that the mother lacks

• mother produces antibodies against the baby’s antigen

• maternal IgG crosses placenta and attacks fetal RBCs

• alloimmune

HDFN lab results

• antibody screens during pregnancy

• cordocentesis for suspected fetus (bilirubin, ab titers)

• can possibly do an intrauterine transfusion

• treate with exhange transfusion after delivery if severe

• prevent with RhIG

Drug induced hemolytic anemia

• can be harmless or severe

• druge or metabolites interact with RBC membrane

• recognized as foreign and antibodies form

• ex: aldomet, penicillin, caphalosporins

• treatment: remove/avoid drugs

Macrovascular hemolytic anemia

• large vessel turbulence

• prosthetic heart valves

• major vessel trauma

• lab: evidence of hemolysis, increased retics, schistocytes, mild anemia

• Non-immune acquired

non immune acquired HA

extrinsic defects

cells are basically normal when produced

hostile condition might be reversible

can be either intra or extravascular

ex: macrovascular, MAHA, TTP, HELLP, DIC, HUS