Post on 21-Jan-2016
RED BLOOD CELL DISORDERS III
By: Dr Abiodun Mark Akanmode MD.
HEMOGLOBINOPATHIES
Genetically determined abnormal hemoglobin synthesis and function.
HbS most common in United States followed by HbC and HbE
SICKLE CELL ANEMIA
Most common familial hemolytic anemia in the world
In malaria endemic parts of Africa - 30% ( protective effect against Plasmodium falciparum)
In United States, 8% blacks are heterozygous for HbS, and 1 in 600 have sickle cell anemia
SICKLE CELL ANEMIA
Autosomal recessive disorder
Intrinsic defect with predominantly extravascular hemolysis, mild intravascular hemolysis
In homozygotes, all HbA is replaced by HbS, whereas in heterozygotes, only about half is replaced
MOTHER & FATHER HAVE SICKLE CELL TRAIT
Normal child 25%
Sickle cell trait 50%
Sickle cell disease 25%
FACTORS AFFECTING SICKLING
Intracellular concentration of HbS >60% is the most important cause of sickling No sickling in heterozygotes with sickle cell trait (HbS
< 50%)
Presence of other hemoglobins: ↓ with HbA/HbF, ↑ with HbC
↑ concentration of deoxy Hb: Red cell dehydration, Acidosis, Hypoxemia
MORPHOLOGY IN HOMOZYGOUS SICKLE CELL DISEASE (HBSS)
In peripheral smears, elongated, spindled, or boat-shaped irreversibly sickled red cells
CONSEQUENCES OF SICKLING IN HOMOZYGOUS SICKLE CELL DISEASE
Severe hemolytic anemia - life span of RBC only 20 days
Microvascular obstructions (Vaso-occlusive crises)
↑ transit time for red cells through the microvasculature (sluggish blood flow in spleen and bone marrow)
↑ expression of adhesion molecules on sickled cells
Inflammation increases adhesion of RBC/WBCs to endothelium
Repeated sickling damages RBC membrane, make them adhere to endothelium
FETAL HEMOGLOBIN (HBF)
↑ HbF at birth prevents sickling in HbSS till 5-6 months of age
Hydroxyurea increases synthesis of HbF
HbF has high affinity for oxygen, prevents sickling
HOMOZYGOUS SICKLE CELL DISEASE
Anemia and vascular stasis lead to hypoxia-induced fatty changes in the heart, liver, and renal tubules
Compensatory hyperplasia of erythroid progenitors in marrow
Bone resorption and secondary new bone formation, resulting in prominent cheekbones and “crewcut” skull
Extramedullary hematopoiesis in liver and spleen
HOMOZYGOUS SICKLE CELL DISEASE In children - moderate splenomegaly, over time hypoxic
damage leads to auto-splenectomy by adulthood
“Autoinfarcted” splenic remnant in sickle cell disease
HOMOZYGOUS SICKLE CELL DISEASE Vascular congestion, thrombosis, and infarction in bones, liver,
kidney, retina, brain, lung, and skin Dactylitis (hand-foot syndrome): painful swelling due to
infarctions in metacarpal bones (aseptic necrosis), mostly infants
Renal papillary necrosis in kidney
HOMOZYGOUS SICKLE CELL DISEASE Hemosiderosis and Pigment Gallstones (calcium
bilirubinate)
Recurrent leg ulcers: commonly around malleoli
Avascular necrosis of femoral head
Proliferative retinopathy → blindness
End-stage renal failure after 40 years of age
Priapism: leading to penile fibrosis and erectile dysfunction
HOMOZYGOUS SICKLE CELL DISEASE
Acute Chest Syndrome Common cause of death in young adults Vaso-occlusion in pulmonary microcirculation Presents with chest pain, dyspnea and lung infiltrates Precipitated by pneumonia, bone infarct with fat embolism
Stroke Common cause of death in children (2-5 yrs) Recurrence rate 70%
HOMOZYGOUS SICKLE CELL DISEASE
Aplastic crisis (associated mostly with parvovirus; no reticulocytes in peripheral blood)
Sequestration crisis (Rapid splenic enlargement with entrapment of sickled RBCs and blood, Reticulocytosis present )
Prone to infections (S. pneumoniae)
Salmonella osteomyelitis
RENAL FINDINGS IN SICKLE CELL TRAIT
Sickling happens in peritubular capillaries in medulla Oxygen tension low enough to cause sickling even with trait
Microhematuria
Renal papillary necrosis
DIAGNOSIS
In homozygous sickle cell disease - irreversibly sickled red cells seen in routine peripheral blood smears
In sickle cell trait - sickling can be induced in vitro by exposing cells to marked hypoxia (Sodium metabisulphite)
TREATMENT Penicillin prophylaxis to prevent pneumococcal
infections
Pneumococcal vaccine, Folic Acid supplementation
Hydroxyurea reduces pain crises and lessens anemia (1) Increases red cell levels of HbF (2) Anti-inflammatory effect due to inhibition of WBC
production (3) Increases red cell size, lowers MCHC (4) Metabolizes to NO (potent vasodilator /inhibits platelet
aggregation)
Allogeneic bone marrow transplantation
APLASTIC ANEMIA. Aplastic anemia is characterized by chronic primary
hematopoietic failure and pancytopenia.
The causes of aplastic anemia includes the following:
-Idiopathic causes.-Chemical agents: carbamazepine, chloraphenicol, gold salts.-Physical agents: full body radiation.-Viral infections: EBV,CMV.-Inherited syndromes: fanconi anemia, telomerase defects.
PURE RED CELL APLASIA.
Pure red aplasia is another marrow disorder in which erythroid progenitors are suppressed.
Its associated with B19 infection.
Pure red aplasia may also seen in neoplastic conditions like thymomas.
IMMUNOHEMOLYTIC ANEMIAS(IHA)
Group of extrinsic hemolytic anemia's with extravascular or intravascular hemolysis.
Antibodies may arise spontaneously or be induced by exogenous agents (drugs/ chemicals)
CLASSIFICATION OF IMMUNOHEMOLYTIC ANEMIA'S
Autoimmune hemolytic anemia(AIHA):-Most common type of IHA.-W>M.-AIHA is either warm or cold type.
Drug induced IHA:penicillins,2/3rd generation cephalosporin's.
Alloimmune hemolytic anemia: ABO & Rh hemolytic disease of newborn.
AUTOIMMUNE HEMOLYTIC ANEMIA. Warm Antibody Type (70%)
Primary (idiopathic) Secondary:
B cell neoplasms (e.g., chronic lymphocytic leukemia),
Autoimmune disorders (e.g., systemic lupus erythematosus),
Drugs(e.g., α-methyldopa, penicillin, quinidine) Cold Antibody Type (30%)
Acute: Mycoplasma infection, infectious mononucleosis
Chronic: Idiopathic, B cell lymphoid neoplasms (e.g., lymphoplasmacytic lymphoma)
WARM ANTIBODY IMMUNOHEMOLYTIC ANEMIA'S
Most common immune hemolytic anemia, caused by immunoglobulin G (IgG) active at 37°C
> 60% cases are idiopathic
Opsonization of RBCs by autoantibodies leading to erythrophagocytosis in spleen and elsewhere (Extravascular)
WARM ANTIBODY IMMUNOHEMOLYTIC ANEMIAS
Incomplete consumption (“nibbling”) of antibody-coated red cells by macrophages leads to spherocytes
Positive Direct Coombs test / DAT ( Direct AntiGlobin Test)
COLD ANTIBODY IMMUNOHEMOLYTIC ANEMIA'S
Low-affinity IgM antibodies that bind to RBC membranes only at temperatures < 30°C
Mediated by antibodies to blood group antigen I or i anti – I antibodies seen in Mycoplasma pneumoniae anti – i antibodies are associated with EBV infection
RBCs are phagocytosed by macrophages, mainly in spleen and liver (extravascular hemolysis)
Sludging of blood in capillaries due to agglutination often produces Raynaud phenomenon
AUTOIMMUNE HEMOLYTIC ANEMIAS
HEMOLYTIC DISEASE OF THE NEWBORN(ERYTHROBLASTOSIS FETALIS)
Maternal antibodies cross the placenta and react with fetal red cells causing hemolysis of fetal RBCs
Rh Incompatibility: maternal allo-immunization to fetal red cell antigens (D antigen of Rh blood group)
No problems during first pregnancy, but anti-Rh antibodies may cause problems in subsequent pregnancies
ABO Incompatibility – mostly mother is group O and the fetus is either group A or B ( milder than Rh incompatibility)
HEMOLYTIC DISEASE OF THE NEWBORN(ERYTHROBLASTOSIS FETALIS)
Kernicterus: staining of basal ganglia and other CNS structures by unconjugated bilirubin
Still birth
Hydrops fetalis – fetal heart failure with massive generalized edema
HEMOLYTIC ANEMIA'S RESULTING FROM MECHANICAL TRAUMA TO RED CELLS
Macroangiopathic hemolytic anemiaMechanical hemolysis from Aortic Stenosis, Defective cardiac valve prostheses (“the blender effect”)
Microangiopathic hemolytic anemia DIC Malignant Hypertension Systemic Lupus Erythematosus Thrombotic Thrombocytopenic Purpura Hemolytic Uremic Syndrome Disseminated Cancer
MICROANGIOPATHIC HEMOLYTIC ANEMIA
MALARIA Plasmodium falciparum, malariae, vivax and
ovale
Transmitted by the bite of female Anopheles mosquitoes
Humans are the only natural reservoir
The parasites destroy large numbers of infected red cells, thereby causing a hemolytic anemia
Massive splenomegaly and occasional hepatomegaly
CEREBRAL MALARIA
Infection of RBCs with P. falciparum induces positively charged surface knobs which bind to adhesion molecules on activated endothelium
Trapping of RBCs in post-capillary venules, especially cerebral vessels in children
Rapidly progressive; convulsions, coma, and death usually occur within days to weeks
BLACKWATER FEVER
Massive intravascular hemolysis
Hemoglobinemia
Hemoglobinuria
Jaundice