Hematology Chapter 22 Extrinsic Defects - Nonimmune Causes

What is HUS? What causes it?

HUS (Hemolytic Uremic Syndrome) is a microangiopathic hemolytic anemia (MAHA) characterized by:

• Hemolytic anemia

• Thrombocytopenia

• Acute kidney injury (renal failure)

The classic cause is infection with Shiga toxin-producing Escherichia coli (E. coli O157:H7), often after ingestion of undercooked hamburger or contaminated food. The toxin damages endothelial cells, especially in the kidneys, leading to microthrombi formation, RBC fragmentation, and platelet consumption.

Classic Triad

• MAHA

• Thrombocytopenia

• Renal failure

Blood Smear

• Schistocytes

What is TTP? What causes it?

TTP (Thrombotic Thrombocytopenic Purpura) is a microangiopathic hemolytic anemia caused by deficiency of the enzyme ADAMTS13.

Normally ADAMTS13 cleaves large von Willebrand factor (vWF) multimers. When ADAMTS13 is deficient, unusually large vWF multimers accumulate and promote platelet aggregation and microthrombus formation. These thrombi shear RBCs as they pass through small vessels, producing schistocytes.

Classic Pentad

• Fever

• Neurologic symptoms

• Hemolytic anemia

• Thrombocytopenia

• Renal dysfunction

Key Laboratory Finding

• Normal PT and aPTT (helps distinguish TTP from DIC)

What does HELLP stand for?

HELLP Syndrome

H = Hemolysis
EL = Elevated Liver Enzymes
LP = Low Platelets

HELLP is a severe complication of pregnancy that often occurs during late pregnancy or postpartum and is associated with preeclampsia and hypertension. Patients typically have schistocytes due to MAHA.

• Hemolysis

• Elevated AST/ALT

• Thrombocytopenia

• Hypertension

• Schistocytes

What could cause allo-immune hemolytic anemia?

Alloimmune hemolytic anemia occurs when a person produces antibodies against someone else's red blood cells.

Common causes include:

Blood Transfusion Reactions

• Recipient develops antibodies against donor RBC antigens.

Hemolytic Disease of the Fetus and Newborn (HDFN)

• Maternal antibodies cross the placenta and destroy fetal RBCs.

These are immune-mediated hemolytic anemias caused by exposure to foreign RBC antigens.

What is a DAT?

DAT = Direct Antiglobulin Test (Direct Coombs Test)

Purpose:

• Detects antibodies and/or complement attached directly to a patient's RBCs.

Used to Diagnose

• Autoimmune hemolytic anemia

• Hemolytic transfusion reactions

• Hemolytic disease of the newborn

Positive DAT

• Antibodies or complement are coating RBCs.

Negative DAT

• Suggests a nonimmune cause of hemolysis.

Can drugs cause anemia?

Yes.

Drugs can cause hemolytic anemia through several mechanisms.

Immune-Mediated Mechanisms

The drug triggers antibody formation against RBCs.

Examples:

• Penicillin

• Cephalosporins

• Methyldopa

Direct Toxic Effects

Some drugs and chemicals directly damage RBC membranes.

Chapter 22 specifically identifies drugs and chemicals as causes of extrinsic nonimmune hemolytic anemia.

Drug-Induced Oxidative Injury

Some medications may trigger hemolysis in susceptible patients (such as those with G6PD deficiency).

What is the hallmark peripheral smear finding in microangiopathic hemolytic anemia

Spherocytes

Schistocytes

Target cells

Elliptocytes

Schistocytes

Schistocytes are fragmented RBCs produced when cells are mechanically damaged in small vessels.

Which syndrome is classically associated with Shiga toxin-producing E. coli infection?

TTP

HELLP

HUS

PNH

HUS

Deficiency of ADAMTS13 is the underlying cause of which disorder?

DIC

TTP

HUS

AIHA

TTP

TTP results from decreased ADAMTS13 activity, allowing large vWF multimers to accumulate.

HELLP syndrome stands for:

Hemolysis Elevated Liver enzymes Low Platelets

Hemorrhage Elevated LDH Low PT

Hemolysis Elevated Leukocytes Low Platelets

Hemoglobin Elevated Liver proteins Low PT

Hemolysis Elevated Liver enzymes Low Platelets

Which organ system is most severely affected in HUS?

Kidneys

Lungs

Skin

Pancreas

Kidneys

Acute renal failure is a major feature of HUS.

A patient has schistocytes, thrombocytopenia, prolonged PT, prolonged aPTT, and decreased fibrinogen. Which disorder is most likely?

TTP

HUS

DIC

PNH

DIC

Which finding helps distinguish TTP from DIC?

Schistocytes

Hemolysis

Normal PT and aPTT

Thrombocytopenia

Normal PT and aPTT

TTP generally has normal PT and aPTT, unlike DIC.

Mechanical destruction of RBCs by prosthetic heart valves produces what type of hemolysis?

Microangiopathic

Macroangiopathic

Immune

Inherited

Macroangiopathic

Large mechanical surfaces such as prosthetic valves cause macroangiopathic hemolysis.

What test detects antibodies or complement attached to a patient's RBCs?

PT

DAT

Osmotic fragility

G6PD screen

DAT

The Direct Antiglobulin Test (DAT) detects immunoglobulin or complement coating RBCs.

A runner develops hemoglobinuria after long-distance running. What mechanism is responsible?

Alloimmune hemolysis

Foot-strike mechanical trauma

G6PD deficiency

Hypersplenism

Foot-strike mechanical trauma

Repeated mechanical trauma to RBCs in capillaries of the feet can cause hemolysis.

Which organism produces Maltese cross forms on a peripheral blood smear?

Plasmodium falciparum

Babesia

Trypanosoma

Leishmania

Babesia

Babesia may produce tetrads known as Maltese crosses.

Which parasite commonly demonstrates ring forms and crescent-shaped gametocytes?

Babesia

Plasmodium falciparum

Toxoplasma

Leishmania

Plasmodium falciparum

P. falciparum is known for ring forms and crescent gametocytes.

Can drugs cause hemolytic anemia?

No

Only in children

Yes, by immune or toxic mechanisms

Only with overdoses

Yes, by immune or toxic mechanisms

Some drugs cause immune-mediated hemolysis, while others may directly damage RBCs.

Which laboratory finding is expected in most forms of hemolytic anemia?

Decreased reticulocyte count

Increased reticulocyte count

Decreased LDH

Increased haptoglobin

Increased reticulocyte count

The marrow responds to RBC destruction by releasing more reticulocytes.

What is the major mechanism causing RBC destruction in MAHA?

Complement fixation

Mechanical shearing by fibrin strands

Iron deficiency

Membrane protein defects

Mechanical shearing by fibrin strands

RBCs are fragmented as they travel through vessels containing fibrin strands and microthrombi.