RBC Path Flashcards
What is Anisocytosis vs. Poikilocytosis?
Anisocytosis: change in blood cell size
Poikilocytosis: change in blood cell shape
Marker on Pluripotent stem cells in bone marrow.
CD34+
Top two causes for chronic blood loss.
- GI bleeding
2. Irregular Menstrual Bleeding
Major cause of anemia due to decreased hematopoiesis.
Iron Deficiency
Giemsa stain feature of anemia due to iron deficiency.
Microcytic/Hypochromic
-RBCs are normally similar in size to lymphocytes
Stain used to detect iron in a blood sample.
Prussian Blue
Describe the lab tests for Iron Deficiency anemia:
- Serum Fe:
- Serum Ferritin:
- Serum Total Iron Binding Capacity (TIBC):
- Transferrin Saturation:
- Decreased
- Decreased
- Increased
- Low
Describe Plummer Vinson Syndrome.
Condition with esophageal webs, and iron deficiency anemia. It most usually occurs in postmenopausal women
Two major causes of megaloblastic anemia.
- Vit. B12 deficiency
2. Folic Acid Deficiency
What is pernicious anemia?
Autoimmune destruction of parietal cells in the stomach. This leads to decreased intrinsic factor secretion and no absorption of B12 leading to megaloblastic anemia
Characteristic of neutrophils in megaloblastic anemia.
Hypersegmented nuclei due to inability to divide.
What 3 categories of chronic diseases can lead to megaloblastic anemia?
- Chronic Infectious Disease
- Chronic Autoimmune Disease
- Malignant Neoplasms
Describe the lab tests for anemia due to chronic diseases and explain why these values are observed:
- Serum Fe:
- Serum Ferritin
- TIBC:
- Transferrin Saturation:
- Decreased or normal
- Normal or Increased
- Decreased
- Normal
The defect is in iron incorporation into Hb molecules during erythropoiesis.
Ferritin can increase because it is an acute phase protein that rises early in inflammation (infection). This is also why serum iron levels can be decreased b/c they are bound to the excess ferritin
What is aplastic anemia?
Anemia due to damaged bone marrow stem cells. All 3 myeloid lineages are affected.
- Erythroid
- Myeloid Granulocyte
- Megakaryocyte
What is Fanconi Anemia.
Aplastic anemia due to an autosomal recessive defect in DNA repair of bone marrow stem cells.
Disease association of Pure Red Cell Aplasia.
Thymoma
-usually causes an autoimmune reaction that also affects RBC precursor cells
What is Myelophthisic Anemia.
Low blood cell count because the bone marrow space is replaced by scar tissue or neoplasms. Decreases the amount of the bone marrow stem cells and the ability for mature blood cells to exit the marrow cavity.
Characteristic blood cell shape in Myelophthisic Anemia.
Dakryocytic Cells
How can organ failure lead to anemia?
Kidney failure leads to decreased erythropoietin production.
Giemsa stain characteristic in cases of Hemolytic Anemia.
Schistocytes
-RBC fragments from lysed RBCs
What lab values are expected in any hemolytic anemia:
- Hb levels
- Haptoglobin
- Lactate Dehydrogenase levels
- Reticulocyte Levels
- Decrease
- Decrease
- Increased (lysed RBCs release the major energy producing enzyme they have)
- Incraesed
2 sites of extravascular hemolytic anemias.
Liver and Spleen
-RBC components usually get stuck in these organs causing hepatomegaly and splenomegaly
Primary cause of Hereditary Spherocytosis leading to hemolytic anemia.
Mutated Spectrin protein (others exist but are less common)
-forms a very fragile RBC
Gold Standard to detect Hereditary Spherocytosis.
Osmotic Fragility
-increased in this disease due to fragile sphere shaped RBCs
What occurs in hemolytic crisis?
If the hemolytic anemia is bad enough:
-fever, abdominal pain, jaundice, low blood pressure, shock
How does a Glucose-6-Phosphate Dehydrogenase def. lead to hemolytic anemia.
Lack of this enzyme leads to decreased NADPH production and inability to produce reduced glutathione. The RBC then has no protection from ROSs and lyses early.
Giemsa stain characteristic of G6PD deficiency hemolytic anemia.
Heinz Bodies
- RBCs have tons of globs of protein in the cytoplasm
- actually causes splenic macrophages to “bite” chunks of the cells leading a RBC characteristic characteristic
What two things can cause an Acquired G6PD deficiency.
Anti-malarial drugs
Sulfa Drugs
Pathology of Sickle Cell Disease
Mutation of Glutamate to Valine at position 6 of the beta globin chain in Hb.
How does Sickle cell disease do to the spleen?
Causes an “Auto Splenectomy” due to multiple infarctions of sickled RBCs blocking blood flow to the spleen.
What type of microbial infections are more common in sickle cell disease?
Encapsulated organisms, due to the loss of spleen function.
What type of microbial infection can cause an Aplastic Crisis in patients with Sickle Cell Disease.
Parvovirus Infection
Gold Standard to Diagnose Sickle Cell Disease.
Hemoglobin Electrophoresis
Why are Beta Thalassemias more common, but alpha thalassemias more serious?
The Beta globin chain only has 2 genes acquired from parents. The chances of both being mutated is much higher than for alpha which has 4 genes.
Alpha is more serious because ALL forms of Hb have alpha globin chains.
Describe the 2 forms of Beta thalassemia.
Both have decreased production of Beta globin chains in Hb
- Thalassemia Minor: heterozygote mutation is not serious and usually only manifests during some other crisis
- Major: patients experience crises often. Skull can show a “crew cute” appearance because even the flat bones in the skull try to produce RBCs
Describe the 4 forms of Alpha Thalassemia.
- One Deletion: silent, no symptoms
- Two deletions: trait carrier, usually symptoms only arise in crisis state from some other cause
- Three Deletions: Hb H formation, severe disease causing hemolytic crisis
- Four Deletions: hydrops fetalis, child dies in utero, Hemoglobin Barts
Giemsa Stain characteristic of RBCs in patients with Thalassemias.
Target Cells
Describe a Direct Coombs Test and why it’s used.
Uses “Anti-human Abs” which recognize host auto Abs against red blood cells. Used to detect Autoimmune hemolytic anemias (AIHA).
Pathology of Warm AIHA.
Surface auto Abs (mostly IgG) opsonize RBCs. This causes destruction of RBCs by two processes. First is destruction of opsonized RBCs in the spleen, second is conversion of the RBC into spherocytes making them more fragile as the circulate.
Condition associated with Warm AIHA.
Chronic Lymphocytic Leukemia (most common type of leukemia)
Pathology of Cold Aglutinin AIHA.
Surface auto Abs (mostly IgM which binds better at cold temps) opsonize RBCs. When temperatures warm up IgM is released but the complement stays bound to the RBCs causing destruction in the spleen or liver.
Two infectious agents associated with Cold Aglutinin AIHA.
- Adenovirus
2. Mycoplasma pneumoniae
What is a major cause of hemolytic anemia due to trauma?
Heart valve prosthesis defect. Trauma lyses the RBCs leading to formation of schistocytes.
Pathology of Paroxysmal Nocturnal Hemoglobinuria.
RBCs are produced that lack CD55/CD59. Without these surface proteins the RBCs cannot inactivate the complement in the spleen and liver and these RBCs are lysed in these organs.
Major compilcatoin of Paroxysmal Nocturnal Hemoglobinuria.
Hypercoagulable state with thrombi forming in the portal or cerebral veins.
How is von Willebrand Disease different from most other bleeding disorders like hemophilia?
Bleeding in vW disease is primarily from mucous membranes
Characteristic bleeding seen in Hemophilia (both A and B) and laboratory tests that are abnormal.
Hemarthrosis is common (joint space bleeding)
aPPT is increased in both since intrinsic pathway factors are lower in production. Factor VIII (A) and Factor IX (B).
Pathology of Disseminated Intravascular Coagulation.
DIC is secondary to some other disease process leading to activation of the coagulation system. Thrombi are produced throughout the circulation leading to ischemia in certain areas. This results in activation of the fibrinolytic system and with the loss of clotting factors the disease leads to intense bleeding.
Tx for DIC
Replace Fibrinogen (cryoprecipitate)
Most common cause of Non-thrombocytopenic purpura.
This is an abnormality of blood vessel walls, not coagulation factors. Mostly due to collagen disorders like scurvy, Ehlers Danlos. Labs are normal.
Cause of Post transfusional thrombocytopenia.
Presence of Anti-PL(A1) Abs in a recipient that is PL(A1) negative.
Pathology of Idiopathic Thrombocytopenic Purpura
Similar to AIHA, there are auto-Abs against platelets (mostly IgG).
Pathology of Microangiopathic Hemolytic Anemia.
Fibrin forms in the peripheral blood vessels lysing RBCs into shcistocytes
Triad associated with Hemolytic Uremic Syndrome.
Hemolytic Anemia
Thrombocytopenia
Renal Failure
Pathology and Presentation of Thrombotic Thrombocytopenic Purpura (TTP).
Defect in ADAMTS13 protein that normally cleaves vWF. Leads to prolonged and excessive clotting and consumption of clotting factors.
Patients present with a pentad: -Hemolytic Anemia -Thrombocytopenia -Renal Failure -Fever -neurological defects (only hematological emergency)
Pathology of Bernard-Soulier Syndrome
Defect in GP IbIX proteins preventing platelets from binding to subendothelial collagen (vWF).
Pathology of Glanzmann Thromasthenia
Defect in GP IIb-IIIa proteins preventing platelets from binding to each other to form plug (aggregation).
Most common acquired form of defective platelet function.
NSAID abuse