EXTRINSIC DEFECTS

EXTRINSIC RBC DEFECTS  HEMOLYTIC ANEMIA  Special tests - YES

- B2 came from B1
LABORATORY TESTS Thalassemia minor – microcytic - Are they equal? = NO
 Basic test Thalassemia major – hemolytic anemia
 Can be counted manually
RBC – *low levels, patient has anemia Carrier protein of B1 – Albumin
Hgb DECREASED or NORMAL RETIC COUNT = Bone marrow problem B2 – will go to the intestines for further breakdown
CBC Hct INCREASED RETIC COUNT = hemolytic anemia  Will be converted into urobilinogen
WBC – *anemia is not a diagnosis, but a syndrome  Urine  urobilinogenuria
MPV
RDW
*Retic count Biliribinuria – problem with liver, biliary obstruction habang
MCV lumalabas yung B2
MCH
MCHC
INTRINSIC – problem in the RBC
ü Cytometric method – classify anemia (microcytic anemia, B1 – cannot exit; non-soluble - Kernicterus
EXTRINSIC – outside the RBC
macrocytic anemia, normocytic, normochromic) B2 – has exit; water soluble
 May be a problem in plasma, blood vessel wall (endothelial lining)
ü Normocytic & Normochromic – where hemolytic anemia falls
 RBC is normal
RBCI ü Reticulocyte count – index of hematopoiesis
o Compensate to red blood cell in peripheral blood Significance of Hemoglobinuria
ü Hemolytic anemia – destruction of RBC  Intravascular Hemolysis
o Spleen – graveyard of cells Hemoglobinopathies are classified as hemolytic anemia
o Loss of RBC, Bone marrow will compensate
RPI – destruction of RBC due to bone marrow Bilirubinuria = biliary obstruction
Electrophoresis – diagnosing hemoglobinopathies and thalassemia Antibody immunoglobulin bind to normal RBC = forming immune complex
 Immune complex  activated complement system  attack RBC  RBC lyse Hemosidenuria = intravascular hemolysis
Spherocyte - Hallmark poikilocytes of hemolytic anemia Urobilinogenuria = extravascular hemolysis
 Sign of hemolysis
Hemolysis:
PBS Schistocytes – fragmented red blood cells Extravascular lysis – graveyard (spleen); left side of abdominal cavity
INTRAVASCULAR  Ab-mediated hemolysis – phagocytosis or complement-
OR mediated destruction
HEMOLYTIC ANEMIA EXTRAVASCULAR
BMA & BMB – to validate  Destruction of RBC before their normal 120-day life span with anemia
Serum Fe
Serum Ferritin
IRON STUDIES TIBC CAUSES: separate mechanism and diverse entities whose common clinical feature is
 No role in diagnosing hemolytic anemia hemolysis ETIOLOGIES OF HEMOLYSIS
 Applied in differentiating micro hypo chromic anemia INTRINSIC EXTRINSIC
HEMOLYSIS Basic routine test for hemolysis
 Inherited protein deficits  Immune-mediated hemolytic anemia
 TB B1:B2 CLINICAL SIGNIFICANCE: - Lead to increased destruction in - Abs + RBCs = IC
o If patient is undergoing hemolysis  Spectrum from chronic to life-threatening membranopathies - Phagocytosis ADCC
o Particularly B1  Always considered in patients with unexplained normocytic or macrocytic anemia - Complement mediated lysis
o B2 – opposite bilirubin
o Elevated B1  Enzymopathies
o Manifestation: PATHOPHYSIOLOGY: - Hemolysis due to overwhelming  Non-immune – walang antibody
 Hyperbilirubinemia - jaundice  Intravascularly oxidative stress or decreased - Microangiopathic hemolytic anemia
 Urobilinogen – by product of conjugated bilirubin  Extravascularly energy production (MAHA)
o Urine and stool specimen  More common - Infections
 Haptoglobin – carrier of free-hemoglobin - Direct trauma
o Main carrier of free hemoglobin  Hemoglobinopathies - Drug-induced hemolysis
o Decreased level in plasma - Lead to splenic destruction SCD
 Inside the bloodstream
o There is a limit and normal value - Likely multiple mechanism of
 Direct cellular destruction – toxins, trauma or lysis
o Not being produced forever destruction
 Fragmentation hemolysis – extrinsic factors produce shearing
o Hemoglobin cannot be excreted in the urine and rupture of RBCs
o Excess free hemoglobin – hold in free iron  Oxidative hemolysis – protective mechanism of cells are CLINICAL PRESENTATION IF HEMOLYSIS IS SUSPECTED
o Transferrin – normal carrier protein of iron overwhelmed  Jaundice
INTRAVASCULAR ACUTE
 Hemopexin – carrier protein of free-iron in the blood  Hemoglobinuria in the presence of anemia
(extrinsic)
 LAD
What are the intravascular measures?  HSM
CHRONIC
If you have hemolytic anemia, what will happen to hemopexin levels? It - Haemoglobinaemia  Cholestasis
will DECREASE - Methaemalbuminaemia  Choledocholithiasis
- Haemoglobinuria  Fatigue
- haemosidenuria OTHER
 Dyspnea
** Haptoglobin and hemopexin = decrease in times of hemolysis PRIMARY NONSPECIFIC
 Outside the bloodstream; spleen – major organ  Hypotension
EXTRAVASCULAR SYMPTOMS
 Sequestration and phagocytosis – due to poor RBC  Tachycardia
deformability  Medical diagnosis
Methemoglobin – ferric is changed, ferric is oxidized (3+) o Inability to change shape enough to pass through HISTORY INCLUDE
 Medications
the spleen KNOWN
 Personal or family history of hemolytic anemia
PHYSICAL  Identify associated condition
If you have hemolytic anemia, what will happen to meth heme albumin EXAMINATION  Infections or malignancies
levels? It will INCREASE Heme oxygenase – enzyme inside spleen converted to biliverdin Complete Review Systems
(green pigment)
HEMATURIA – intact RBC, seen in microscopic analysis, cloudy
HEMOGLOBINURIA – lysed RBC, clear urine INITIAL WORK UP
CBC (anemia) Normo-Normo or Macrocytic
Biliverdin reductase – convert to bilirubin B1
Reticulocyte count
B1; LDH – not common
 Methemalbumin
Haptoglobin
 Hemoglobinuria – tested by reagent strip test If you have hemolysis, do you have hyperbilirubinemia? UA
 Hemosiderinuria – presence of hemosiderin in urine - YES LDH Intracellular, and levels increase when RBC rupture
o Hemosiderin from hemoglobin - Secondary to B1 elevation
HAPTOGLOBIN Binds to free hemoglobin, and levels decrease in hemolysis
o Form of iron in the urine - Because in the liver it becomes conjugated
B1 Levels rise as its production exceeds elimination capability
RETIULOCYTOSIS Unless significant IDA or marrow suppression is present
CAUSING
In hemolysis, do you expect elevated B2?
EXTRINSIC DEFECTS
MACROCYTOSIS
Hemoglobinuria
UA
Absence of these findings should prompt a search for other causes CLINICAL FEATURES: similar to other MAHA syndromes
SUPPORTIVE
Initiated after hemolysis is confirmed
CARE
For abnormal RBCs TREATMENT: discontinuing the offending agent, providing supportive care, plasma exchange
Spherocytes is not beneficial
PBS
Schistocytes
Bite or blister cells MICROANGIOPATHIC HEMOLYTIC ANEMIA (MAHA)
 Caused by membrane deficits or repeated small membrane MECHANISM: RBC fragment  schistocytes due to trauma from an endovascular device or
removals by macrophages microthrombi

SPHETOCYTES
SPHEROCYTOSIS – not a diagnostic for hemolytic anemia because CAUSES:
both hereditary spherocytosis and immune etiologies may cause 1. Thrombotic MicroAngiopathies (TMAs)
anemia - Diverse group of clinical entities that share MAHA as a central feature
 Fragmented cells that result from intravascular destruction - Thrombotic thrombocytopenic purpura
SCHISTOCYTES
 Occurs in MAHA syndromes - Hemolytic uremic syndrome
 Result from partial phagocytosis 2. Other microangiopathic hemolytic anemia syndromes
BITE AND
 Occur in oxidative causes
BLISTER CELLS
 G6PD Deficiency THROMBOTIC MICROANGIOPATHIES (TMAs)
Further differentiates immune causes of hemolytic anemia from  Thrombitic thrombocytopenic purpura
DAT
nonimmune causes

IMMUNE HEMOLYTIC ANEMIA DEFECT: reduced or absence of ADAMTS13 enzyme activity

 AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)

 Approximately 95% of TTP cases are associated with acquired autoantibodies

MECHANISM: autoantibody-mediated destruction  Often without an inciting event or disorder

HALLMARK: positive DAT result TTP – life-threatening and requires timely diagnosis and treatment

CAUSES: HALLMARKS OF TTP:

 Idiopathic o Thrombocytopenia
 Viral and bacterial infection o Fever
 Autoimmune conditions o Renal injury
 Connective tissue disorder o MAHA
 Lymphoproliferative malignancies o Neurologic dysfunction
 Blood transfusion
LABORATORY FINDINGS:
 Transplantations
 Negative DAT result
AIHA Two primary subgroups based on binding temperatures  Normal coagulation testing
WARM AIHA COLD AIHA Assessment of ADAMTS13 enzyme activity is diagnosing for TTP
 More common than cold AIHA  Cold agglutinin disease  Result usually delayed
 Making a presumptive diagnosis imperative

MECHANISM: IgG autoantibodies reaction MECHANISM: IgM autoantibodies reaction

with RBC protein antigens with RBC polysaccharide antigens causing PLASMIC SCORE – used to predict severely reduced ADAMTS13 enzyme activity and initiate
lysis on rewarming by complement fixation early treatment
and intravascular hemolysis TREATMENT:
 IgG coated RBCs removed by  Plasma exchange and glucocorticoids
reticuloendothelial macrophages and  Plasma exchange removes affected platelet
sequestered in the spleen, sometimes  Associated with infectious or malignant  Autoantibodies while replenishing ADAMTS13 enzyme levels
leading to splenomegaly processes
o Mycoplasma pneumonia
o Mononucleosis PLASMA EXCHANGE IS SUPERIOR = FFP infusion is beneficial and should be started if
TREATMENT: TREATMENT: transfer to a plasma exchange-capable center is delayed
o Glucocorticoids o Supportive measures
o Management of the underlying o Avoidance of triggers OTHER MICROANGIOPATHIC HEMOLYTIC ANEMIA SYNDROMES
condition o Underlying disease management
o Blood transfusion
o Supportive care

HEMOLYTIC TRANSFUSION REACTIONS

CAUSE: alloantibodies that reacts with incompatible RBCs
CLINICAL SIGNIFICANCE: Hemolysis can range from acute to delayed, and can be life-
threatening

DRUG-INDUCED IMMUNE HEMOLYTIC ANEMIA

 Rare

MECHANISM: drug-induced antibody formation a DAT result is positive in patients with this
condition

TREATMENT: involves removal of the offending agent

DRUG INDICED THROMBOTIC MICROANGIOPATHY (DI-TMA)

MECHANISM: drug induced antibodies formation or direct toxicity causing formation of
placement microthrombi