Hemolysis溶血作用

Red Cell Destruction by the Reticuloendothelial System
CO (expired)
RBC
Transferrin
Amino Acid Pool
Fe Hb Globin
RE Cell
Bilirubin
Liver
Urobilinogen
Intravascular Red Cell Hemolysis
Pathobiology of the membrane lesion in HS
Abnormalities of the cytoskeletal proteins lead to vertical uncoupling, with vesicle formation and loss of pieces of membrane, leading to shape change and loss of elasticity.
RBC
Globin
Hemoglobin Dimer
Hemoglobin Tetramer
Methemoglobin
Haptoglobin
HEPATOCYTE
Hemopexin
Heme
Fe
Bilirubin
Methemalbumin
Hemoglobin Methemoglobin
Hemosiderin
>3 (with 1 being baseline)
We search for hemoglobin breakdown pigments indicative of hemolysis
Scleral Icterus
Jaundice due to increased bili pigment – best seen in the sclerae
environment?
Classification of Hemolytic Anemias
Intracellular Defects
Membrane defect Metabolic defect Hemoglobin abnormality
Case # 1
A 55 yo man was seen for increasing fatigue over several months His wife noticed he had yellow eyes His physician noted that his spleen was palpable 5 cm below the LCB His Hgb was 8 gm and his retic ct was 15%. Bilirubin was 3.0 T, 2.5 Ind (elevated)
52 † Complications post splenectomy
40
Gall stones
Anemia
Splenectomy
Intermittent jaundice
15
12
10
7
Cardinal Features of Hereditary Spherocytosis
Increased rate of red cell destruction Spherocytosis Splenomegaly Familial occurrence Invariable benefit fromUrobilinogen
Intravascular Hemolytic Event
Hemoglobinuria
Serum Haptoglobin
Hemosiderinuria
0
1
2
3
4
5
6
10
Indicators of Intravascular Hemolysis
Absence of haptoglobin Presence of free hemoglobin in serum Hemoglobinuria (acute) Hemosiderinuria (chronic) Absence of hemopexin Presence of methemalbumin
After examining the peripheral smear and calculating the reticulocyte index
We measure
LDH Bilirubin
– The unconjugated bilirubin is elevated with extravascular hemolysis
Intracellular Defects
Membrane defect Metabolic defect Hemoglobin abnormality
Case # 2
An 18 yo healthy African American male had the sudden onset of nausea, fever, abdominal pain and dark urine Four days previously he had taken large doses of acetaminophen for a flu-like illness PE showed scleral icterus Hgb 8 g, Retic ct 12% Heinz Body prep+ When questioned carefully, he recalled similar symptoms after a urinary tract infection treated with sulfamethoxazole about 5 yrs ago
Splenomegaly
One of the most constant features of extravascular hemolysis It is caused by accelerated destruction of red cells, mediated by macrophages in the spleen, and sometimes the liver
Pigmented Gall Stones
From increased bilirubin content of the bile, if the process is chronic.
Polychromasia
Reticulocytes contain a large amount of RNA which stains bluish red on a standard blood smear. Because there is a shift of marrow retics into the PB, there is polychromasia. Also look for shape changes.
So, once we have determined that hemolysis is causing the anemia,
how do we determine what is causing the hemolysis?
Is it a problem intrinsic to the red cell, or is the red cell merely an innocent bystander in a hostile
Intravascular – within blood vessels
Plays little or no role in normal red cell destruction, but plays a major role in certain types of hemolytic anemia Causes hemoglobinuria and/or hemosiderinuria
“Blister” cells with acute hemolysis after an oxidant stress in G6PD Deficiency
From Hoffbrand, Pettit and Moss
Heinz Body Preparation
G 6 PD deficiency
The distinguishing feature of the hemolytic anemias is the increased rate of destruction of circulating red cells.
Hemolytic anemias are recognized by anemia with signs of increased red cell production which occurs as the normal bone
Learning Objectives
Distinguish extravascular from intravascular hemolysis Recognize hemolytic anemia by its clinical and laboratory features Diagnose the common types of hemolytic anemias
marrow attempts to compensate for the accelerated loss of RBC’s.
Peripheral smear – polychromasia
Reticulocytosis with an elevated RPI
Changes in RBC morphology
Most common inherited RBC enzyme deficiency Affects over 400 million people world wide. Highest gene frequencies found in tropical and subtropical countries where the deficiency offers protection against falciparum malaria Is an example of balanced polymorphism Discovered in 1956