Red Blood Cell and Bleeding Disorders Flashcards
What are microcytic hypochromic anemias dur to?
disorders of Hb synthesis
What are macrocytic anemias due to?
things that impair maturation of erythroid precursors in marrow
What are the principal clinical features of extravascualr hemolytic anemias?
anemia, splenomegaly, and jaundice
- patients need splenectomy
What are the principal clinical features of intrinsic hemolytic anemias?
anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, and jaundice.
*do not need splenectomy
What morphology is seen in hemolytic anemias regardless of cause and type?
- increased # of erythroid precursors
- Prominent reticulocytosis
- hemosiderosis in spleen, liver, LN
- Extramedullary hematopoiesis
- bilirubin gallstones
What is the name of the disorder in which there are intrinsic defects in the red cell membrane?
Hereditary Spereocytosis
*autosomal dominant 75% of the time
What proteins are defective in hereditary sperocytosis?
ankyrin, spectrin, band 3, protein 4.2
What tests are positive in hereditary sphercytosis?
osmotic fragility +
What are the presenting symptoms of hereditary spherocytosis?
Anemia, splemomegaly, and jaundice
What are the labs on hereditary spherocytosis?
increased MCHC, increased RDW
What are patients with hereditary spherocytosis at risk of?
aplastic crisis that is triggered by parvo B19 virus
Treatment of hereditary spherocytosis?
splenectomy
What is the inheritance of G6PD?
autosomal recessive- males at risk!
Why is G6PD needed?
To reduce NADP-> NADPH which is needed to regenerate reduced glutathione.
What two populations are affected by G6PD most often?
black- modest reduciton in G6PD
mediterrean- marked reduction in G6PD activity
What are the common triggers for oxidant stress?
Infection, foods (fava beans), drugs
What cells will a peripheral smear show in G6PD?
- RBSc with Heinz bodies and bite cells.
- Heinz cells are removed by splenic macrophages that result in bit cell formation
What are the genetics of sickel cell anemia?
Autosomal recessive
- point mutation glu-> val in the sixth codon of beta-globin
Sickel cell trait is protective against what?
Falciparum malaria
Why are newborns with sickle cell disease initially asymptomatic?
HbF is protective and no HbS is present for first few months of life
What is the pathogenesis of sickle cell disease?
low O2, dehydration, or acidosis precipitates sickling, which results in anemia and vaso-occclusive disease
What does peripheral blood smear show in a patient with sickle cell disease?
sickled cells, reticulocytosis, and target cells, howell-jolly bodies
What are the sites of extramedullary hematooiesis?
- skull and facial bones “crew-cut appearance and chipmunk facies”
- -hepatomegaly
What are patients with SSD and infection with parvo B19 at risk for?
aplastic crisis
SSD patients with autosplenectomy are at risk for what?
- bacterial infections from encapsulated organisms.
- Strep and H. influ (most common cause of death in children)
- Salmonella osteomyelitis
How does acute chest syndrome associted with SSD present?
- vaso-occlusion in pulmonary microcirculation.
- chest pain, SOB, lung infiltrates
What is a common presenting symptom in a young individual with SSD?
dactylitis-> painful hand swelling due ot vaso-occlusion
How is the diagnosis of SSD confirmed?
Metabisukfite reagent that induces sickling
What is the name of the disease that results in a decrease in synthesis of globin?
Thalassemia
What type of anemia do the thalassemias cause?
microcytic, hypochromic
What are the mutations that cause beta thalassemia?
point mutations in splice sites and promoter sequences.
What are the two types of beta thalassemia and which is more common?
Major and minor
Minor more common
What will a peripheral smaer in a patient with beta thalassemia minor show?
hypochromia, microcytosis, basophilic stippling and target cells.
How does beta thalassemia major present?
within 6-9 months of birth as Hb switches from HbF to HbA
What will a peripheral smear show in a patient with beta thalassemia major?
- severe red cell abnormalities, microcytosis and hypochromia
- Target cells, basophilic stippling, and fragmented red cells
Where can the extramedullary hematopoiesis be seen in patients with beta thalassemia major?
- spleen/liver-> HSM
- skull-> “crewcut” appearance on xray
What do almost all patients with beta thalassemia major develop?
secondary hemochromotosis
What is the genetic cause of alpha thalassemias?
inherited deletions.
Where is beta thalassemia most common?
Mediterranean countries, parts of Africa, and SW Asia
What is the name of the unpaired gamma chains that form tetramers in newborns with alpha thalassemia?
Hemoglobin barts
How is the clinical syndrome of alpha thalassemia classified?
By the number of alpha globin genes that are deleted
What do one and two alpha globin gene deletions produce?
- one: asymptomatic silent carrier
- two: alpha thalassemia trait , mild anemia, cis deletion increases risk of severe thalassemia in offspring
What does three alpha globin gene deletions produce?
- Hemoglobin H disease, tetramers of HbH form, tissue hypoxia develops, intracellular inclusions form that promote red cell sequestration.
- moderately severe anemia
What does four alpha globin gene deletions produce?
- Hydrops fetalis->lethal in utero.
- fatal unless intrauterine transfusions are performed.
What is the mutation and what protein is affected in Paroxysmal Nocturnal Hemoglobinuria?
- mutations in the PIGA gene that encode for the GPI anchor
- three proteins that make up the anchor are deficient;DAF (CD55), C8 binding protein, CD59.
What is causing the RBC damage and lysis is Paroxysmal Nocturnal Hemoglobinuria?
compliment
Why do RBCs have a tendency to lyse at night is Paroxysmal Nocturnal Hemoglobinuria?
shallow and slower respirations cause an increase in CO2 and decrease in pH causing the cells to become damaged and lysed by compliment
What do patients develop with paroxysmal nocturnal hemoglobinuria?
mild to moderate anemia with hemosiderinuria that will eventually lead to iron deficiency.
What are patients at risk for with paroxysmal nocturnal hemoglobinuria?
thrombosis–> major cause of death
What does the indirect Coombs test for?
- tests for presence of antibodies in the patients serum.
- agglutination will occur if serum antibodies are present
What does the direct Coombs test for?
- test for presence of antibody or complement coated RBCs.
- agglutination will occur if antibodies or complement have coated RBCs already
What is the warm antibody type of immunohemolytic anemia?
- IgG mediated, coats RBCs
- Partially removed in the spleen-> spherocytes
- moderate splenomegaly
- penicillin and methyldopa
What is the cold antibody type of immunohemolytic anemia?
- IgM antibodies bind to RBCs at lower temperatures.
- following mycoplasma pneumonia, EBV, CMV, influenza, HIV
- fingers, toes, ear, nose
What can cause microangiopathic hemolytic anemia?
-prosthetic heart valves, HUS, TTP, malignant HTN, and SLE
What is the common theme among megaloblastic anemias?
impairment of DNA synthesis that leads to ineffective hematopoiesis.
What is the morphology in megaloblastic anemia?
- RBCs will be macrocytic and oval shaped “macro-ovalocyte”
- lack central pallor
What is anemia due to a B12 deficiency called?
pernicious anemia
What are some underlying causes of B12 megaloblastic anemia?
autoimmune gastritis, achlorhydria, gastrectomy, EPD, ileal reseciton, tape worms, B12 deficiency
What are the lab findings in B12 megaloblastic anemia?
- hypersegmented granulocytes
- decreased B12
- increased homocysteine
- increased methylmalonic acid
What is the most common cause of B12 megalobalstic anemia?
Pernicious anemia caused by autoimmune gastritis.
What is a complication of B12 deficiency if not treated?
- Subacute combined degeneration of the spinal cord.
- peripheral neuropathy
- dorsal column (proprio/ vibra)
- LCST (spasticity)
What are the three main causes of anemia of folate deficiency?
decreased intake, increased requirement, impaired utilization
What can interfere with folate absorption?
oral contraceptives and phenytoin
What are the labs of anemia of folate deficiency?
-decreased folate, increased homocysteine, normal methymalonic acid
What type of anemia is Iron deficiency anemia?
Microcytic, hypochromic
Who is most commonly affected by Iron deficiency anemia?
toddles, adolescent girls, and women of childbearing age
What are the common etiologies of Iron deficiency anemia?
Chronic bleeding (GI, menorrhagia), malnutrition/ absorption, increased demand (pregnancy)
What are the lab findings in iron deficiency anemia?
decreased ferritin, increased TIBC, decreased serum Fe, decreased % saturation.
What does a peripheral smear in a patient with Iron deficiency anemia show?
Microcytic, hypo chromic RBCs, with central pallor.
What can long term Iron deficiency cause?
Koilonychias, alopecia, glossitis, intestimal malabsorption
What syndrome can occur with iron deficiency anemia and what is it characterized by?
Plummer-Vinson Syndrome: anemia, dysphagia, and esophageal webs.
What are some initial presenting symptoms in Iron deficiency anemia?
Fatigue, conjunctival pallor
What is anemia of chronic disease?
anemia associated with chronic inflammation or cancer.
What is released in anemia of chronic disease that causes the sequestration of Fe?
Acute phase reactants are released from the liver, including hepcidin, which results in the sequestration of Fe in cells.
What specific cytokine is associated with stimulation of hepcidin?
IL-6
What are the lab values in anemia of chronic disease?
increased ferritin, decreased TIBC, decreased serum Fe, decreased % saturation.
What is the underlying cause of aplastic anemia?
Damage to hematopoietic stem cells, resulting in pancytopenia.
What are the common etiologies of aplastic anemia?
drugs, chemicals, viral infections, and autoimmune damage.
What does the bone marrow show in aplastic anemia?
hypocellular marrow with fatty infiltration
What are the most common viral agents associated with aplastic anemia?
Parvo B19, HIV, HCV, EBV
What are some of the clinical findings in a patient with aplastic anemia?
- progressive weakness, pallor, dyspnea.
- ecchymoses and petechiae
- bacterial infections
What is red cell aplasia?
primary marrow disorder in which only erythroid precursor cells are suppressed.
What is myelophthisic anemia?
form of marrow failure in which space-occupying lesson replace normal marrow elements
What is the cause of a relative polycythemia?
hemoconcentration due to decreased plasma volume (dehydration, burns)
What is the underlying cause of absolute polycythemia?
increase in total red cell mass, high EPO levels, decreased O2 saturation–> lung disease, congenital heart disease, high altitude
What does PT assess and what factors are in this pathway?
Common and Extrinsic pathway, factors I,II,V,VII,and X
What does PTT assess and what factors are in this pathway?
Common and Intrinsic pathway, factors XII,XI, X, IX, VIII, V, II, I
How is thrombocytopenia defined?
platelet count less than 100,000
What are the 4 major ways in which thrombocytopenia can develop?
decreased platelet produciotn, decreased platelet survival, sequestration, and dilution
What do the autoantibodies attack in immune thrombocytopenic purpura?
IgG antibodies attack platelet antigens, specifically GPIIb-IIIa
What does the marrow show in immune thrombocytopenia purpura?
increased number of megakarycytes
what are the lab findings in immune thrombocytopenic purpura?
decreased platelet count, increased megakaryocytic, normal PT/PTT
How is Immune thrombocytopenic purpura diagnosed?
diagnosis of exclusion.
What is the major cause of acute immune thrombocytopenic purpura?
- occurs in children after a viral illness-> 1-2weeks later.
- self limited and resolves
What is the pathogenesis of HIT?
- development of IgG antibodies against heparin bound platelet factor 4 (PF4) leading.
- Heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia
What are the symptoms of TTP?
fever, transient neurologia deficits, microangiopathic anemia, thrombocytopenia, renal failure
What are the symptoms of HUS?
microangiopathic hemolytic anemia and thrombocytopenia,
What is the distinguishing factor between TTP and HUS?
HUS does not have neurological symptoms and frequently occurs in children
What is the genetic mutation associated with TTP?
ADAMTS13- normally degrades vWF
What is cause of “typical” HUS?
infection with E.coli O157:H7
What is Bernard-Soupier Syndrome?
- defective adhesion of platelets to subendothelial matrix.
- Inherited deficiency in GpIb-IX
What is Glanzmann Thrombasthenia?
-defect in platelet aggregation due to deficiency in GpIIb-IIIa
What are the presenting symptoms of Von Willebrand Disease?
Spontaneous bleeding from mucous membranes, excessive bleeding from wounds, menorrhagia
What are the genetics of vWD?
autosomal dominant
What is the role of vWF?
- vFW acts to carry/ protect factor VIII
- vFW deficit does not allow normal platelet adhesion
What are the labs in vWD?
normal platelet count
increased bleeding time
can have increase in PTT
What is Hemophilia A?
Factor VIII deficiency
What are the genetics of Hemophilia A?
X-linked Recessive
What are the labs in Hemophilia A?
Prolonged PTT
Normal PT
What is Hemophilia B?
Christmas Disease, Factor IX deficiency
What are the genetics of Hemophilia B?
X-linked Recessive
What are the labs of Hemophilia B?
Prolonged PTT
Normal PT
What is DIC?
Excessive activation of coagulation and the formation of thrombi in the microvasculature
What are the labs in DIC?
Decreased platelet count
increased bleeding time
increased PT/PTT
What is released in sepsis that is a mediator of DIC?
TNF
What are some of the common causes of DIC?
obstetric complications*
endothelial injury
malignant neoplasms
major trauma
What are some common presenting symptoms of DIC?
-Microangiopathic hemolytic anemia, dyspnea, cyanosis, respiratory failure, convulsions and coma, sudden or progressive circulatory failure
