MLAB 1415: Hematology
Keri Brophy-Martinez
Hemolytic Anemia: Nonimmune Defects
Nonimmune Hemolytic Anemia


These anemias represent a group of
conditions that lead to the shortened survival
of red cells by various mechanisms.
Causes

Antagonists



Hemolysis precipitated by either injury to the RBC
membrane or to denaturation of hgb
Toxins, infectious agents
Physical trauma

Hemolysis caused by physical injury to RBC
Antagonists: Infectious Agents

Parasites: Intracellular infections

Malaria





Carried by mosquito
Release of the parasite from the cell causes cell lysis
Species of malaria include:

Plasmodium vivax

P. faciparum - most fatal

P. malariae - uncommon

P. ovale - uncommon
Peripheral smear examination will reveal intracellular parasites

Morphology depends on the species
Babesiosis


Tick-borne
Peripheral smear examination will reveal intracellular parasites

Resemble tiny rings inside the RBC
Antagonists: Infectious Agents

Bartonellosis




Transmitted by sand fly or direct inoculation by
scratch or bite of a mammal
Restricted to South America
Induces pitting or invagination or RBC membrane
Clostridium perfringens


Bacteria is OUTside the RBC
Exotoxin production affects integrity of host cell
membrane
Antagonists

Venoms


Some spiders contain enzymes that lyse the red
cell membrane (i.e Brown Recluse)
Snake venoms can lysis by:



Directly disrupting the RBC membrane
Altering RBC membrane to cause complement
activation
Initiate DIC
Physical Injury or Trauma

Intravascular and/or extravascular hemolysis

Striking abnormal shapes of the circulating
blood, such as fragments and helmet cells
Physical Injury or Trauma

Categories

Microangiopathic hemolytic anemia


HUS, TTP,DIC, Hypertensive crisis
Other physical trauma


Burns
Macroangiopathic hemolytic anemia

Cardiac prosthesis, exercise-induced hemoglobinuria
Microangiopathic hemolytic anemias
(MAHAs)



Fragmentation of the red cells by fibrin strands
as they pass through abnormal arterioles.
The fibrin strands are the results of intravascular
coagulation
Damaged RBC cleared by extravascular
hemolysis
Types of MAHAs




Hemolytic uremic syndrome= HUS
Thrombotic Thrombocytopenic Purpura= TTP
Hypertensive Crisis
DIC
HUS: Hemolytic Uremic Syndrome



Multisystem Disorder
Triad of clinical findings
 Hemolytic anemia with RBC fragments
 Thrombocytopenia
 Acute nephropathy
Classified based on presence or absence of diarrhea
 Atypical HUS
 Found in adults
 Absence of diarrhea
 D+ HUS
 Onset between 6 months- 5 years
 Majority of cases
 Presence of diarrhea
Pathophysiology of D + HUS





90% of cases associated with Shiga toxin
produced by E. coli 0157:H7
Organism enters human GI tract, damages the
mucosa and releases toxin
Toxin activates the platelets
Platelet thrombi trap RBCs and fragment then
Platelet thrombi block glomerular vasculature
resulting in renal failure
D+ HUS
Clinical Findings








Foul-smelling and bloody diarrhea
Onset acute
Sudden pallor
Abdominal pain
Vomiting
Jaundice
Hematuria
Possible acute renal failure
TTP:
Thrombotic Thrombocytopenic Purpura





Platelets and VWF aggregate on the
microvascular endothelium
As RBC are forced through the aggregates,
fragmentation occurs
Platelets are removed from the circulation
Affects young adults, especially females
Systemic infections, autoimmune disorders, and
pregnancy are common precipitating factors
Lab Features in HUS and TTP
Evidence of Hemolysis
Decreased H and H
Increased reticulocytes/polychromasia
Thrombocytopenia
Leukocytosis with left shift
Schistocytes
Evidence of Intravascular Hemolysis Hemoglobinemia
Hemoglobinuria
Decreased haptoglobin
Increased total & unconjugated bilirubin
Evidence of Thrombotic
Microangiopathy
Thrombocytopenia
DIC:
Disseminated Intravascular Coagulation




Bacterial sepsis, neoplasms, immunologic
disorders or trauma can precipitate DIC
As coagulation is activated, fibrin is deposited in
the microvasculature
RBC become trapped in the fibrin meshwork and
then fragment
Due to the clotting process- platelets are
consumed
Hypertensive Crisis





Increase in blood pressure damages endothelial
cells
Platelets and coagulation factors are activated
Fibrin deposits in the vasculature
RBCs fragment on the fibrin strands.
Peripheral smear shows RBC fragments, low
platelet count, mechanism unknown
Macroangiopathic Hemolytic
Anemias & Burns



Cardiac prosthesis (heart valves)
 RBCs fragment as they pass through prosthetic heart valves
 Peripheral smear shows RBC fragments, helmet cells and occasional
spherocytes
March hemoglobinurea/ Exercise-Induced
 Caused by traumatic destruction of the red cells in strenuous and
sustained physical activity such as marching or running
Burns
 Warming RBCs to 49o C induces fragmentation
 It is thought that the direct effect of the heat on spectrin, causes the red
cells to fragment and burst.
 Spleen clears damaged RBCs within 24 hours of injury
Referenes


McKenzie, S. B. (2010). Clinical Laboratory Hematology
(2nd ed.). Upper Saddle River, NJ: Pearson Education,
Inc.
Rodak, B. F. (2002). Hematology Clinical Principles and
Applications (3rd ed.). St. Louis: Saunders Elsevier.