RBC Pathology

Question 1

What are the 4 steps of Primary Hemostasis?

Answer 1

1. Transient Vasoconstriction: mediator by nerves and endothelin
2. Platelet Adhesion to surface of disrupted vessel: vWF (on vessel wall) binds GPIb (on platelet)
3. Platelet Degranulation: ADP (encourages exposure of GPIIb/IIIa), TXA2 promotes aggregation
4. Platelet Aggregation

Question 2

What is normal platelet count?

Answer 2

150-400 K/uL

Question 3

What are the functions of vWF, GpIIb-IIIa, and GpIb. What deficiencies are associated with each one?

Answer 3

vWF: located on endothelial cells, bindsto GpIb on platelets so they can adhere to damaged endothelium

GpIb: located on platelets, binds vWF, def. is called Bernard-Soulier

GpIIb-IIIa: located on platelets, binds fibrinogen, links platelets to each other, def. is Glanzmann Thrombasthenia

Question 4

Patient presents with mucosal bleeding, low platelet counts, increased megakaryocytes on biopsy with normal PT/PTT. Treatment with corticosteroids resolves the condition. What would serum Ab tests reveal?

Answer 4

Immune Thrombocytopenic Purpura

-would see AutoAbs to platelet antigens like GpIIb-IIIa

Question 5

Patient presents with Skin and mucosal bleeding, low platelets, normal PT/PTT, increased megakaryocytes, fever, and CNS abnormalities. Biopsy shows anemia with schistiocytes. What is the pathogenesis of this condition?

Answer 5

Thrombocytopenic Purpura (microangiopathic hemolytic anemia)

• autoAb binds and decreases ADAMTS13 (cleaves vWF for removal of clot)
• many microthrombi form on endothelial cells and RBCs get sheared and lyse.

Question 6

Patient presents with Skin and mucosal bleeding, low platelets, normal PT/PTT, increased megakaryocytes, fever, Renal Insufficiency. Biopsy shows anemia with schistiocytes. Gram stain reveals gram(-) rod What is the pathogenesis of this condition?

Answer 6

Hemloytic Uremic Syndrome (microangiopathic hemolytic anemia)
-EHEC O157:H7 toxin damaged endothelial cells and causes microthrombi formation that lyses RBCs

Question 7

Describe intrinsic clotting cascade

6 steps

Answer 7

Tissue damage activates Hageman Factor (XII)

1. XIIa activates XI
2. XIa activates IX
3. IXa combines with VIIIa to activate X
4. Xa combines with Va to activate II (prothrombin) w/ calcium
5. IIa (thrombin) activates I (fibrinogen) forming fibrin fibers
6. XIIIa cross links the fibrin fibers

Question 8

Describe the extrinsic clotting cascade

4 steps

Answer 8

Trauma activates VII

1. VIIa combines with IIIa to activate X
2. Xa combines with Va to activate II (prothrombin) w/ calcium
3. IIa (thrombin) activates I (fibrinogen) forming fibrin fibers
4. XIIIa cross links the fibrin fibers

Question 9

Describe clot dissolution

Answer 9

1. Tissue Plasminogen Activator (tPA) activates plasminogen

2. Plasmin degrades the fibrin clot

Question 10

Function of alpha2 antiplasmin

Answer 10

inactivates free plasmin (does nothing to plasmin already bound and inactivating fibrin)

Question 11

Most important circulating thrombin inhibitor

Answer 11

Antithrombin III

Question 12

Why does Warfarin induce a hypercoagulable state early on in its use?

Answer 12

Warfarin inhibits vit. K epoxide reductase

• this inhibits many clotting factors
• however, it also inhibits protein S and protein C formation
• Protein S activates Protein C and protein C inactivates VIII and V
• so without these two protein, VIII and V would remain highly active forming lots of clots

Question 13

Patient presents with bruises that do not heal. He says that his grandfather had the same problem and died in the OR. What is the inheritance pattern and what would lab values reveal?

Answer 13

Hemophilia (either A or B)

• X-linked recessive
• A is VIII and B is IX
• PTT elevated, normal PT
• normal platelets and bleeding time

Question 14

What would PTT, PT, and bleed time lab values be in vWF disease?

Answer 14

PTT increased: factor VIII half-life is increased by vWF, without it the VIII is not very effective
PT normal
Bleed Time increased

Question 15

Treatment for vWF disease

Answer 15

Desmopressin: increases vWF release from platelets

Question 16

What is the best test and what laboratory findings are there in DIC?

Answer 16

Decreased platelet counts, increased PT and PTT, decreased fibrinogen, elevatd D-dimer (best test)

Question 17

Treatment for disorders of overactive fibrinolysis (lack of alpha2 antiplasmin or urokinase release from prostatectomy)

Answer 17

Aminocaproic Acid: blocks plasminogen activation

Question 18

What is Virchow’s Triad?

Answer 18

Three major risk factors for thrombosis

1. Disruption of blood flow
2. Endothelial Damage
3. Hypercoagulable state

Question 19

Function of Thombomodulin

Answer 19

Binds thrombin and activates protein C (which binds with protein S to inactivate factors V and VIII)

Question 20

Symptoms of Factor V Leiden disease

Answer 20

Mutated form of factor V that doesn’t bind protein C, so it is highly active and leads to hypercoagulable state

Question 21

What is the mean corpuscular volume in microcytic anemias?

Answer 21

less than 80um^3

Question 22

Function of Hepcidin

Answer 22

Sequesters iron in storage sites so that bacteria cannot use iron to survive.

Question 23

Pathology of Anemia of Chronic Disease

Answer 23

Liver produces acute phase proteins (including hepcidin). Hepcidin forces the body to continue keep iron in storage. This makes it unavailable for the body to use. The result is anemia (but ferritin will be increased and TIBC will be decreased).

This is a result of some chronic disease like an autoimmune disease or endocarditis.

Question 24

Patient presents with weakness, fatigue, and dyspnea. Conjunctiva are pale and the patient has headaches and lightheadedness. Laboratory findings include high ferritin, decreased TIBC, increased serum iron and increased % saturation. The physician suspects a congenital cause of anemia. What enzyme is deficient?

Answer 24

Sideroblastic Anemia

• defective aminolevulinic acid synthase (ALAS) which is a defect in protoporphyrin synthesis
• biopsy shows iron-laden mitochondria surrounding the nuclei (ring sideroblast)

Question 25

How do alpha thalassemias present in terms of gene mutation?

Answer 25

one mutation (asymptomatic) two, mild anemia three: severe anemia, beta chain form tetramers four: lethal, death in utero

Question 26

Patient presents with weakness, fatigue, and dyspnea. Conjunctiva are pale and the patient has headaches and lightheadedness. Head X-ray shows a "crew cut" appearance. What is the pathogenesis of this disease?

Answer 26

Beta Thalassemia - two forms, minor and major - major results in alpha tetramers that aggregate and damage RBCs - leads to expansion of erythropoiesis in the skull bones (crew cut appearance)

Question 27

What is the mean corpuscular volume in macrocytic anemia?

Answer 27

greater than 100um^3

Question 28

Patient presents with weakness, fatigue, and dyspnea. Conjunctiva are pale and the patient has headaches and lightheadedness. Labs reveal increased homocysteine, hypersegmented neutrophils, and glossitis. What medication might this patient be on?

Answer 28

Folate Deficiency Megaloblastic Anemia -methotrexate can cause this (folate transfers a methyl to B12 which transfers it to homocysteine to make methionine) -body cannot make methionine which is needed for DNA synthesis and cell division

Question 29

The 3 major neutrient deficiency anemias are absorbed where in the GI tract?

Answer 29

Iron: duodenum Folate: jejunum B12: ileum (bonded with instrinsic factor)

Question 30

Microbe notable for causing B12 deficiency.

Answer 30

Diphyllobothrium latum (fish tapeworm)

Question 31

Folate deficiency results in increased homocysteine. B12 also results in increased homocysteine but also what other precursor?

Answer 31

Methylmalonic Acid -increase in this impairs spinal cord myelination (this is important for differentiating the two)

Question 32

What are reticulocytes and how are they used in the clinic?

Answer 32

Immature RBCs with a bluish cytoplasm (RNA). Normally 1-2% in serum but they do increase in response to anemias and hemorrhage. However if they are less than 3% in a crisis, then suspect poor marrow response.

Question 33

Patient presents with weakness, fatigue, and dyspnea. Conjunctiva are pale and the patient has headaches and lightheadedness. The cells do not pass the osmotic fragility test. What is the pathogenesis of these RBCs and the treatment?

Answer 33

Hereditary Spherocytosis - involves spectrin, ankyrin, or band 3.1 proteins - loss of membrane structure and sphere rigid cell shapes Tx: splenectomy

Question 34

African American patient presents with painful joints after exercising. Blood smear easily confirms diagnosis. What is the pathogenesis of this condition and what is the treatment?

Answer 34

Sickle Cell Disease - autosomal recessive glutamate replaced by valine at position 6 on the beta globin chain - HbS cells aggregate when deoxygenated Tx: hydroxyurea- increases production of HbF to prevent sickling

Question 35

How can you tell the difference between extravascular and intravascular hemolysis?

Answer 35

Extra: usually leads to jaundice, splenomegaly, and gallstone risk Intra: increased haptoglobin (protein that binds the Hb released from lysed RBCs)

Question 36

Sickle Cell disease causes increased risk by these 3 organisms

Answer 36

Autosplenectomy increased encapsulated organism infection: - Strep pneumo - H. flu Also salmonella typhi causing osteomyelitis

Question 37

Patient presents with weakness, fatigue, and dyspnea. Conjunctiva are pale and the patient has headaches and lightheadedness. He also has shallow breathing that is rapid due to acidotic state. He says it is worse at night. What is the marker missing and what is the pathogenesis of this disease?

Answer 37

Paroxysmal Nocturnal Hemoglobinuria - lack of CD55 (DAF) - RBCs and WBCs need DAF to protect from complement degradation, the disease lacks an anchoring protein (GPI) that prevents insertion of DAF into the membrane - in PNH this is missing and complement destroys blood cells

Question 38

Patient presents with hemoglobinuria and back pain. He recently returned from a trip to Africa where he received primaquine medication to take care of malarial infection. What would be seen on blood smear and what is the pathogenesis?

Answer 38

Glucose-6-Phosphate Dehydrogenase Def. - Heinze bodies with bite cells - patients cannot reduce glutathione (needed for oxidative protection) - precipitated by oxidative stressors (primaquine, sulfa drugs, fava beans, dapsone)

Question 39

Patient presents with weakness, fatigue, and dyspnea. Conjunctiva are pale and the patient has headaches and lightheadedness. Cold agglutinin test and direct coombs test are positive. What is the pathogenesis of this condition?

Answer 39

Autoimmune Hemolytic Anemia - usually due to IgG binding RBCs and destruction in the spleen - (if it was warm agglutinin it would be IgM with intravascular hemolysis)

Question 40

Describe Direct and Indirect Coombs tests

Answer 40

Direct: detects presence of Abs on RBCs -IgG is added to patients serum and if agglutination occurs it is (+) Indirect: detects Abs in patients serum -Anti IgG mixed with patient's serum looking for agglutination

Question 41

What is aplastic anemia?

Answer 41

Damage to hematopoietic stem cells resulting in pancytopenia. Can be caused by drugs or other radiation that damages bone marrow.

Question 42

What is a myelophthisic process

Answer 42

Some pathologic process that replaces marrow with fibrosis. Hematopoiesis is impaired. Results in pancytopenia.