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Hematology Flashcards

1
Q

What are the cellular components of blood?

A

RBCs (erythrocytes)

WBCs (leukocytes)

Platelets (thrombocytes)

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2
Q

What is in the soluble component of blood (plasma)?

A

Electrolytes

Proteins

Lipids

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3
Q

How are blood cells different from other cells of the body?

A

Short life span (except lymphocytes)

Multiplicity of cell types

Widely distributed

BM must respond quickly to needs for additional cells

Stem cells must be maintained

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4
Q

What is hematopoiesis?

A

Formation and development of blood cells and other formed elements (RBCs, platelets too)

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5
Q

What is the average life spans of RBCs, granulocytes, platelets?

A

RBC = 4 months

Granulocytes <10 hours

Platelets = 1 week

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6
Q

How can you identify hematopoietic stem cells morphologically?

A

You cannot identify them in bone marrow smear

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7
Q

What is the potency of hematopoietic stem cells?

A

Pluripotent

Repopulate all cellular lineages - erythroid, myeloid, lymphoid, platelets

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8
Q

Where is the initial site of primitive hematopoiesis?

A

Yolk Sac

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9
Q

What is the first site of definitive hematopoiesis?

A

liver

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10
Q

What is the progression of hematopoiesis locations?

A

Yolk sac - liver - bone marrow and spleen

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11
Q

What is the predominant blood forming organ after birth?

A

Bone marrow

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12
Q

How do stem cell divisions occur to preserve self-renewal and differentiation?

A

Asymmetrically more often - 1 cell divides into stem cell and commited cell

Not as common is symmetric - 1 cell divides int 2 stem or commited cells

This is regulated by stromal cells, growth factors

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13
Q

What distinguishes precursor cells from hematopoietic stem cells and hematopoietic progenitor cells?

A

ARE morphologically identifiable

No self-renewal capacity (although progenitor cells don’t either)

Uni-potent only - committed to 1 lineage

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14
Q

What cell type of hematopoeisis is most active in the cell cycle?

A

Precursor cells - mitotically active

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15
Q

What is the normal myeloid to erythroid ratio?

A

3-3.5:1

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16
Q

What areas have hematopoeitic capabilities throughout ontogeny?

A

Yolk Sac

Aorta-gonad-mesonephros (AGM) region

Liver

Spleen
Bone marrow

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17
Q

What are the two things that can happen to make someone anemic?

A

Problem in bone marrow (failure of production)

Peripheral destruction

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18
Q

What information does a bone marrow biopsy provide that an aspirate cannot?

A

Architecture of the bone marrow

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19
Q

What are reticulocytes?

A

Slightly larger, slightly bluer red blood cells that have just left the bone marrow (polychromasia)

Good indicator of bone marrow dysfunction

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20
Q

What is the reticulocyte count?

A

Percentage of reticulocytes (number of reticulocytes per 100 RBC’s)

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21
Q

What is the absolute reticulocyte count?

A

Actual number of reticulocytes in given volume of blood (retic. count * #RBCs)

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22
Q

What does the absolute reticulocyte count tell you?

A

Bone marrow production

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23
Q

What are normal number of red blood cells in blood?

A

5-6 million

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24
Q

What is a normal absolute reticulocyte count?

A

50-100,000 reticulocytes/uL/day

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25
Q

What is the WHO definition of anemia?

A

Hgb < 13gm% in men

Hgb <12gm% in women

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26
Q

What is wrong in this bone marrow aspirate?

A

Acute leukemia

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27
Q

What is myelophthisis?

A

Infiltration of marrow with something that shouldn’t be there (metastatic cancer, for instance, or TB)

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28
Q

What is leukoerythroblastosis?

A

Presence of immature young red and white cell precursors in blood (where they don’t belong)

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29
Q

What is leukoerythroblastosis a sign of?

A

Something infiltrating the marrow - something is causing the cells to leave before they are mature

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30
Q

What can be used to stimulate blood cell production in bone marrow patients?

A

Recombinant erythropoietin (in case of kidney failure, for instance)

Thrombopoietin agonists

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31
Q

What is aplastic anemia?

A

Anatomic and physiologic failure of bone marrow that results in loss of hematopoietic cells from the bone marrow with fatty repacement of bone marrow (aplasia) and reduction, below normal, of WBC, RBC and platelet counts (pancytopenia)

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32
Q

What does this bone marrow biopsy reveal?

A

Aplasia

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33
Q

What is the peak incidence age of aplastic anemia?

A

mid 20s, decreased incidence above 60 years old

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34
Q

What people have higher incidence of aplastic anemia?

A

Far east have 2-4x higher incidence

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35
Q

What are some etiologies of aplastic anemias?

A

Acquired

Inherited

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36
Q

What are some drugs that are always associated with aplastic anemia?

A

Chemotherapies

Benzene

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37
Q

What are some drugs that are sometimes associated with aplastic anemia?

A
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38
Q

What are some viruses that infect bone marrow cells?

A

Parvovirus

Herpesvirus (CMV, EBV)

Retrovirus (HIV)

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39
Q

What ist he mechanism of parvovirus mediated bone marrow failure?

A

Direct cytotoxicity

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40
Q

What is the mechanism of bone marrow failure in EBV infection?

A

Immune mediation

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41
Q

What is the mechanism of bone marrow failure in dengue virus infeciton?

A

Inhibition of growth

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42
Q

What is the mechanism of bone marrow failure in CMV infection?

A

Accessory cell target

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43
Q

What hepatitis is responsible for hepatitis-associated BM failure?

A

non-A, non-B, non-C

2-3 months after acute hepatitis

2-5% of patients with aplastic anemia have history of hepatitis

Probably immune mediated

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44
Q

What is important about hepatitis associated BM failure with respect to how it can be treated?

A

Responds to immunosuppression

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45
Q

What molecular phenomenon has been identfied in 30-50% of patients iwth acquired aplastic anemia?

A

Shortened telomeres

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46
Q

What is the working hypothesis of acquired aplastic anemia?

A

Results from immune dysregulation of hematopoiesis caused by (asymptomatic) viral infections or environmental toxins

Drugs, chemicals and viruses may interact with cellular components, altering normal cellular recognition sites and resulitng in a loss of self-tolerance

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47
Q

What defines severe aplastic anemia?

A

BM biopsy cellularity <25% plus 2 of 3:

Granulocytes <500/ul

Platelets < 20,000/ul

Reticulocyte count < 40,000/ul

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48
Q

What defines very severe aplastic anemia?

A

Severe AA with granulocytes <200/ul

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49
Q

What defines moderate aplastic anemia?

A

Not severe

Stable, depressed counts for > 3 monhts

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50
Q

What is a patient’s survival with aplastic anemia inversely correlated with?

A

Degree and duration of neutropenia

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51
Q

What do patients with apastic anemia die from?

A

Infection - neutropenia

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52
Q

How do you treat aplastic anemia?

A

Withdraw offending agents (drugs)

Supportive care (transfusions, etc, if needed)

Immunosuppression

Stem cell transplant

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53
Q

What is the most common immunosuppression used in aplastic anemia?

A

Antithymocyte globulin (ATG)

Cytolytic to lymphocytes

Can cause an allergic reaction though (serum sickness); very toxic

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54
Q

What is a big risk with immunosuppression treatment in aplastic anemia?

A

20% evolve to MDS/AML at 10 years

10% evolve to overt paroxysmal nocturnal hemoglobinuria

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55
Q

What are benefits of allogenic stem cell transplants in aplastic anemia?

A

It is curative

However, can cause GVHD, secondary malignancies, and can be rejected and hard to come across

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56
Q

What is fanconi anemia?

A

Most common inherited bone marrow failure

Autosomal (and x linked) recessive

Chromosomal instability and hypersensitivity to DNA damage

50-75% have physical abnormalities

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57
Q

What are the physical abnormalities of fanconi anemia?

A

Cafe au lait spots, hyperpigmentation

Short stature, microsomia, hypoplastic or absent thumbs, radial aplasia, microcephaly

Horseshoe kidney, hydronephrosis

Infertility

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58
Q

Why do you need to identify fanconi anemia as the cause of anemia before proceeding with treatment?

A

FA patients are susceptible to DNA damage (impaired repair)

Do not want to irradiate

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59
Q

How do you treat fanconi anemia?

A

Androgens

G-CSF

Modified stem cell transplant (cures BM failure, but does not alter risk of solid tumors

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60
Q

How do you diagnose fanconi anemia?

A

Increased chromosome breakage in lymphocytes cultured with DNA cross linking agents

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61
Q

What term is used for the premature destruction of red blood cells?

A

Hemolysis

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62
Q

What factor will be elevated in folate deficiencies?

A

Homocysteine

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63
Q

What is the origin of megaloblastic anemias?

A

Impaired DNA synthesis

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64
Q

What are the sequellae of B12 and/or folate deficiency?

A

Megaloblastic anemia (you get reticulocytopenia, leukopenia, and thrombocytopenia too)

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65
Q

If anemic, and BM is not the problem, what will you find on blood labs?

A

Elevated absolute reticulocyte count - compensation!

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66
Q

What do you find on bone marrow aspirate in anemias with no issues in the BM (hemolysis)?

A

Erythroid hyperplasia - bone marrow turns on production of red cells

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67
Q

Why do RBCs get destroyed?

A

Poor flexibility through spleen

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68
Q

What do you find in labs in intramedullary hemolysis?

A

Decreased reticulocytes indicative of ineffective erythropoiesis

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69
Q

What is hemolysis?

A

Premature produciton of RBCs

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70
Q

What is extravascular hemolysis?

A

“outside the blood” - by macrophages in reticuloendothelial system (spleen, for instance)

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71
Q

What does the fact that RBC’s are biconcave contribute to their ability to function/

A

Makes them malleable and able to squeeze through tight spaces - deformable

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72
Q

What are RBC’s broken down into?

A

Hemoglobin -> Biliverdin -> Bilirubin

Bilirubin enters to blood as unconjugated; gets conjugated in liver (secreted to bile and blood, some secreted via kidney)

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73
Q

When does unconjugated bilirubin elevate?

A

Hemolysis that exceeds the ability of liver to conjugate it

Elevated bilirubin is sign of active hemolysis

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74
Q

What is elevated unconjugated bilirubin indicative of?

A

Active hemolysis

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75
Q

What occurs in intravascular hemolysis?

A

Hemoglobinemia that gets filtered through kidneys -> hemoglobinuria

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76
Q

When do you see hemoglobinuria?

A

Intravascular hemolysis (also see hemoglobinemia)

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77
Q

When do you see hemoglobinemia?

A

Intravascular hemolysis (also see hemoglobinuria)

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78
Q

When can you see jaundice?

A

Unconjugated bilirubinemia (hemolysis)

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79
Q

What are consequences of hemolysis?

A

Jaundice

Splenomegaly

Marrow erythroid hyperplasia

Reticulocytosis

Increased LDH

Decreased haptoglobin

Hemoglobinemia (intravascular)

Hemoglobinuria (intravascular)

Hemosiderinuria (intravascular)

Coomb’s Test - specific for presence of Abs on surface of red cells

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80
Q

What is the most common antibody produced in immune-mediated hemolysis?

A

IgG - “warm”, extravascular

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81
Q

Why is IgM-mediated hemolysis intravascular?

A

Binds complement, destroyed intravascularly

“cold” Ab affinity is greater at extremities in the cold

Mycoplasma pneumonia - also IgM

Mononucleosis - also IgM

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82
Q

What is a direct Coomb’s Test?

A

Detects presence of antibodies on RBC’s directly (IgM, IgG, complement)

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83
Q

What is an indirect Coomb’s Test?

A

Detects presence of Antibodies in blood that are specific to RBCs (not bound to RBCs though)

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84
Q

What are hereditary hemolytic disorders?

A

Spherocytosis, elliptocytosis

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85
Q

What is the most common enzymatic defect that leads to hemolytic anemia?

A

G6PD deficiency

Oxidant stress (infection, acidosis, meds) leads to precipitation of Hgb on RBC membrane and within RC resulting in intra and extravascular hemolysis

Reticulocytes have higher G6PD, so the hemolysis is self limiting

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86
Q

Why is G6PD hemolysis self-limited?

A

Oxidant stress (infection, acidosis, meds) leads to precipitation of Hgb on RBC membrane and within RC resulting in intra and extravascular hemolysis

Reticulocytes have higher G6PD, so the hemolysis is self limiting

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87
Q

What is DIC?

A

Disseminated Intravascular Coagulation

Formation of blood clots throughout body - microangiopathic (small blood vessels) hemolytic anemia

RBC’s sheared through clots - form schistocytes, see polychromasia, nucleated RBCs

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88
Q

What do you see here?

A

Microangiopathic hemolytic anemia (mechanical trauma)

Can be caused by DIC, Thrombotic thrombocytopenic purpura, Prosthetic heart valvs, eclampsia

RBC’s sheared into schisocytes

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89
Q

What is the most abundant protein in the human body?

A

Hemoglobin

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90
Q

What allows hemoglobin to be packed in such high concentrations in blood?

A

Very soluble

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91
Q

What is the main funciton of hemoglobin?

A

Oxygen (and CO2) transport

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92
Q

What is the main structure of hemoglobin?

A

2 α family and 2 β family globin chains

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93
Q

Where does oxygen bind in hemoglobin?

A

In iron within the heme molecules within the globin chains of hemoglobin (4 chians with 1 heme group each binds a total of 4 molecules of oxygen)

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94
Q

What is significant about the synthesis of α-globin and β-globin?

A

It is balanced - produce the same amount of both

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95
Q

What is the predominant form of hemoglobin in prenatal life?

A

Hgb F - 2α and 2γ chains

(embryonic hemoglobin exists very briefly before then)

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96
Q

What occurs at around birth with respect to hemoglobin?

A

Hemoglobin F to Hemoglobin A switch (α2γ2 to α2β2)

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97
Q

What is the most important function of hemoglobin?

A

Reversibly binds oxygen - grabs on and lets go of it (variable affinity)

Bohr Effect: decreased pH leads to decrease in hemoglobin’s affinity for oxygen (unloading)

2,3, DPG is a glycolysis biproduct, binds to β chain N termini of Hgb molecule, leading to T confirmation and decreased oxygen affinity (unloading)

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98
Q

Why does hemoglobin have decreased affinity for oxygin in tissues?

A

Bohr effect: low pH decreases Hgb affinity for oxygen

2,3 DPG - glycolysis biproduct that binds to β chain N-term of Hgb, leading to taut confirmation and decreased oxygen affinity

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99
Q

What are qualitative hemoglobin disorders?

A

Hemoglobinopathies - defects in the structure

E.g. sickle cell disorder

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100
Q

What are quantitative hemoglobin disorders?

A

Thalassemia

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101
Q

What are hemoglobinopathies?

A

Qualitative disorders of hemoglobin (i.e. structure)

E.g. Sickle Cell Disease

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102
Q

What are thalassemia syndromes?

A

Quantitative defects in Hemoglobin - decreased produciton of normal globin chains

E.g. β-thalassemia

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103
Q

Which populations are more affected by Sickle Cell?

A

African Americans (1 in 500)

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104
Q

Why do WBC’s often get elevated in Sickle Cell Disease?

A

Reticulocytes can be counted as WBC’s on peripheral smear (you have elevated reticulocytes)

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105
Q

What is the cause of Sickle Cell Disease?

A

Point mutation in β-globin gene

Substitution of Valine for Glutamic Acid causing abnormal hemoglobin, known as HgS

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106
Q

What is Hemoglobin S?

A

Abnormal Hemoglobin form found in Sickle Cell

Caused by point mutation in β-globin gene (Val for Glutamic Acid at position 6)

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107
Q

Why does Hgb S cause Sickle Cell Anemia?

A

Hgb S polymerizes into rod-like structures which alters the cell morphology of RBCs

Cause microvascular occlusion - increased adhesion of sickled cells to endothelium

Compromised blood flow (organ infarction) and chronic extravascular hemolysis (by spleen)

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108
Q

Why do you hav evasculopathy in Sickle Cell anemia?

A

Free heme scavenges nitric oxide and causes vasoconstriction, endothelial damage, pulmonary HTN

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109
Q

Why do you have thrombosis in Sickle Cell patients?

A

Flipping of membrane phosphatidylserine lipids exposes negatively charged glycolipids that activate the coagulation cascade

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110
Q

What physiological states promote sickling in Sickle Cell disease?

A

Hypoxia

Infection
Dehydration

Acidosis

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111
Q

Why do chronic hemolysis patients need to have folic acid supplements?

A

Bone marrow needs to be producing more RBC’s. Can’t let them become folate deficient

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112
Q

How do you diagnose Sickle Cell Disease?

A

Prenatal - chorionic villous biopsy, fetal DNA

Post-natal: all newborns screened

Hemoglobin electrophoresis

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113
Q

What do you find on physical exam in Sickle Cell patients?

A

Jaundice, leg ulcerations

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114
Q

What do you find in peripheral blood smear in Sickle Cell patietns?

A

Sickled cells

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115
Q

What CBC abnormalities do you see in Sickle Cell disease?

A

Elevated White

Anemia

Hemoglobin of 7

Low hematocrit

High reticulocyte

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116
Q

How do you treat Sickle Cell Disease?

A

Analgesics, Folic Acid, prophylactic penicillin, vaccinations, avoid dehydration, surveillance

Hydroxyurea increases HgBF adn decreases HgbS)

Iron Chelation

Stem cell transplantation is potentially curative (but risky)

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117
Q

What is Sickle Cell Trait?

A

Clinically normal heterozygous for beta-S globin gene

Hyposthenuria (inability to concentrate urine)

Sudden death in military recruits (and athletes?) has been reported

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118
Q

What is β-thalassemia?

A

β globin chain synthesis is decreased or absent

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119
Q

What is α-thalassemia?

A

α-globin chain synthesis is decreased or absent

All four alpha globin genes are defective - incompatible with life

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120
Q

Where do you see increased incidences of thalassemias?

A

Mediterannean, Middle East, Africa, India, SE Asia

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121
Q

What is β-0-Thalassemia?

A

Complete absence of β globin chian production

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122
Q

What is β-+-thalassemia?

A

Decreased produciton of β globin chain (not total loss)

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123
Q

What is the pathophysiology of β-thalassemia?

A

Unbalanced chain synthesis

Decreased absolute produciton of HgbA causing hypochromic, microcytic anemia

Compensatory increase in non-beta globin chains (HgbF HgbA2)

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124
Q

What do you see on blood smear in β-thalassemia?

A

Hypochromic, microcytic anemia

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125
Q

What happens to the excess α chains in β-thalassemia?

A

Accumulate in RBC’s and form α4 tetramers which precipitate in RBC’s (Heinz bodies)

RBC’s are prematurely destroyed in marrow and outside of marrow

Compensatory increase in marrow erythropoiesis and extramedullary hematopoiesis (hepatosplenomegaly)

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126
Q

What are heinz bodies?

A

Precipitates in RBCs of excess alpha chains of globin seen in β-thalassemia

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127
Q

Where are RBC’s destroyed in β-thalassemia?

A

Marrow (intramedullary hemolysis)

Spleen (extravascular hemolysis)

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128
Q

Why do you see hepatosplenomegaly in β-thalassemia patients?

A

Extramedullary erythropoiesis - would see bone marrow in liver and spleen

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129
Q

What are mainstays of therapy of β-thalassemia?

A

Chronic transfusion therapy with iron chelation (don’t want to have too much iron)

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130
Q

What is α-thalassemia trait?

A

1 alpha glbin gene defective (asymptomatic, silent carrier)

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131
Q

What is α-thalassemia minor?

A

2 α globin genes defective

mild hypochromic microcytic anemia, splenomegaly

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132
Q

What is hemoglobin H disease?

A

3 α globin genes are defective

Hemoglobin H (β4) precipitates in RBCs leading to intramedullary and extravascular hemolysis

Mild to moderate hypochromic microcytic anemia and splenomegaly

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133
Q

What is transfusion medicine?

A

branch of medicine concerned with collection and infusion of blood and blood components

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134
Q

What is the purpose of blood banking?

A

transfusion of correct blood product ot the corrrect patient, at the correct time

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135
Q

What are the components of collected blood?

A

Plasma

platelets

White cells

Red cells

136
Q

Identify the layers

A
137
Q

What is the hematocrit of a unit of RBCs in transfusion?

A

~60%

138
Q

Why do you give patients RBCs?

A

Oxygen carrying capacity

139
Q

What are platelet concentrates?

A

Apheresis units useful to give to patients for clotting

140
Q

Why do you give patients platelets?

A

For clotting

141
Q

How long can you keep RBC’s?

A

42 days in the fridge

142
Q

How long can you keep platelet concentrates?

A

5 days (at room temp)

143
Q

What is the purpose of Fresh Frozen Plasma?

A

Clotting, NOT volume replacement

144
Q

How long does Fresh Frozen Plasma last?

A

1 year (kept forzen)

145
Q

What is cryoprecipitate?

A

Small volume product when you slowly thaw Fresh Frozen Plasma and you take the precipitate

Given for clotting in specific deficiencies

146
Q

What is the difference between plasma and cryo?

A

Cryo has big proteins

147
Q

What is the basis for blood typing?

A

Agglutination - need to be within 20 nm (electrostatic forces), so IgG is not responsible (too small)

This is IgM mediated

148
Q

Schema for hemagglutination

A
149
Q

What is the basis for ABO blood typing?

A

Determined by presence of abscence of enzyme

Type 0 = no enzyme

Type A = N-acetylgalactosaminyl transferase

Type B = D-galactosyl transferase

Type AB = Both

150
Q

What ABO enzyme do type O patients have?

A

No enzyme

151
Q

What ABO enzyme do type A patients have?

A

N-acetylgalactosaminyl transferase

152
Q

What ABO enzyme do type B patients have?

A

D-galactosyl transferase

153
Q

What ABO enzyme do type AB patients have?

A

N-acetylgalactosaminyl transferase (A) and D-galactosyl transferase (B)

154
Q

Where are ABO antigens found?

A

RBC’s, WBCs, Platelets, Epithelial Cells, Spermatozoa, Gastric mucosa

155
Q

Where are ABO antigens secreted?

A

Sweat, Saliva, Semen, Breast milk, Tears, Digestive juices

156
Q

How can ABO typing be used in inheritance?

A

O = OO

A = AA/AO

B= BB/BO

AB = AB

Do the punnet squares

157
Q

What antibodies do type A patients have?

A

Anti-B

158
Q

What antibodies do type B patients have?

A

Anti A

159
Q

What antibodies do type O patients have?

A

Anti A and Anti B

160
Q

What antibodies do AB type patients have?

A

None

161
Q

What is the universal RBC donor type?

A

O

162
Q

What is the univerasl platlet donor type?

A

AB

163
Q

What is Front type testing?

A

Patient RBCs and seperate reagent antibodies (IgM) against A and B

164
Q

What is Back type ABO testing?

A

Patient’s serum/plasma and seperate reagent RBC’s of type A and B antigens

165
Q

What happens if you transfuse the wrong blood type?

A

Anti A and Anti B antibodies are IgM and fix complement, which can cause intravascular hemolysis (acute hemolytic transfusion reaction)

166
Q

What are the Rh blood groups?

A

Blood group composed of ~50 antigens

Most commonly and colloquially refers to the antigen D

Rh+ = have D expression; Rh - = No D expression

167
Q

Why is the Rh blodo typing system important?

A

Highly antigenic - patients will react against it if they are Rh-

168
Q

How do you perform an antibody screen?

A

Patient plasma and reagent RBCs with known RBC antigens at 37C

Wash and incubate with anti-human IgG

If agglutination occurs, antibodies for RBC antigens is present

169
Q

What is a crossmatch?

A

Last check for “compatible” RBCs prior to transfusion (checks ABO compatability)

W/ no atypical antibodies (electronic, immediate spin crossmatch - Donor RBC + patient plasma)

w/ atypical antibodies (RBC from donor + patient plasma (RT, 37C and w/ anti IgG)

170
Q

What are viral complications of transfusion?

A

HIV, HBV, HCV, HTLV, CMV, West Nile

Window period is small since the testing is molecular

HAV, EBV, Parvovirus B19 and others are NOT screened for

171
Q

What are bacterial complications to transfusions in RBCs?

A

Yersinia enterocolitica, pseudomonas fluorescens

They proliferate in cold

172
Q

What are bacterial complications to transfusing platelets?

A

Most organisms can proliferate at storage temperatures

Staph epidermidis, Bacillus cereus

173
Q

What are problems that patients can develop with bacterial infected blood transfusions?

A

Sepsis

Shock from preformed bacterial toxins

174
Q

What are non-viral/non-bacterial infectious complications of blood transfusions?

A

Malaria

Babesiosis

Toxoplasmosis

Trypanosomiasis (Chagas Disease)

Reckettsia (Lyme Disease)

Prions (Mad Cow, CJD)

175
Q

What is acute intravascular hemolysis?

A

Usually due to anti-A and anti-B antibodies

Causes DIC, acute renal failure, shock

176
Q

What is delayed (extravascular) hemolysis?

A

Antibodies to non-self RBC antigens

Causes decreased hematocrit, maybe fever and malaise

177
Q

What is allo-immunization?

A

Antibodies to non-self RBC antigens

For patients with many transfusions, get difficulty obtaining compatible blood and HDN

178
Q

What is iron overload?

A

Seen in patients with lots of transfusions

179
Q

What is non-hemolytic febrile transfusion reactions?

A

Complication seen with transfusions due to leukocytes

180
Q

What is allo-immunization to HLA antigens?

A

Platelet transfusion refractoriness and transplant rejection - Leukocyte mediated transfusion complication

181
Q

What are leukocyte-mediated transfusion complicaitons?

A

Non-hemolytic febrile transfusion reactions

Allo-immunization to HLA antigens

GvHD

Immuno-modulation

182
Q

What is post-transfusion purpura?

A

Anti-HLA antibodies or anti-platelet antigen antibodies causes platelet depletion - causes bruising

183
Q

What are platelet-associated complications in transfusions?

A

Post-transfusion purpura

Refractoriness to platelet transfusions

Allergic-like reactions

184
Q

What are plasma-associated complications of transfusions?

A

Allergic reactions (hives, but can be more severe)

Anaphylaxis (IgE anti-IgA in IgA deficient individuals (rare, but fatal)

Transfusion-related acute lung injury (TRALI) - Anti-granulocyte/anti-HLA antibodies in donor plasma, which causes granulocytes to plug pulmonary vasculature

185
Q

What is TRALI?

A

Transfusion associated acute lung injury

Anti-granulocyte/Anti-HLA antibodies in donor plasma that causes granulocyte plugging of pulmonary vasculature

Non-cardiogenic pulmonary edema

Treat w. aggresive respiratory support including oxygen and mechanical ventilation

Rapid onset (within 6 hours of transfusion)

186
Q

What is one of the most common complications with transfusions?

A

Circulatory overload (must take it into account)

187
Q

What do you do when you suspect a transfusion reaction in a patient?

A

Stop the transfusion

Maintain IV access and administer normal saline

Trat symptoms and report to transfusion service

188
Q

What is hemostasis?

A

Control of bleeding vs control of clotting

Control of bleeding = platelets, fibrin formation

Control of clotting = vessel wall, endogenous anti-coagulant system, fibrinolysis

189
Q

What are the components of the hemostasis system?

A

Platelets
Fibrin-forming system

Fibrinolytic system

Endogenous anticoagulant system

Vessel wall

190
Q

What are platelets/thrombocytes (synonyms)?

A

Anuclear cells wtih 7-10 day lfie span

Typically present in 150-400 x10^3 /ul

Complex structure with many granules with proteins and clotting factors within them

Have important surface receptors (GP Ib and αIIβIII - fibrinogen receptor)

191
Q

What two main surface receptors do platelets have?

A

GP Ib

αIIβIII

192
Q

What is the funciton of platelets?

A

First line of defense in hemostasis at site of vessel injury (form platelet plug) - Adhesion, activation, aggregation

Platform for fibrin formation

Mediate inflammation, vascular constriciton, and fibroblast profileration

193
Q

Where are coagulation factors produced?

A

Liver

194
Q

How do coagulation factors circulate as?

A

Pro-enzymes (zymogens) - need to be activated, and then activate each other

195
Q

Which coagulation factors are cofactors?

A

V, VIII, and HMWK

196
Q

Which coagulation factors require vitamin K for normal biosynthesis?

A

II, VII, IX, X

197
Q

How much of each coagulation factor is required for adequate hemostasis?

A

20-40%, typically

198
Q

What is VonWillebrand Factor (vWf)⇆

A

Glycoprotein with multimers of 2-50 subunits

Prodcued by megakaryocytes (stored in platelet α granules) and endothelial cells

Mediates adhesion to subendothelial collagen via platelet glycoprotein receptor Ib (GPIb)

Carrier for factor VIII - prevents its degradation

199
Q

What prevents the degradation of factor VIII?

A

VonWillebrand Factor

200
Q

What is the goal of hemostasis?

A

Formation of a fibrin clot that plugs up bleedign at the site of vascular injury

201
Q

What is thrombin?

A

Potent protease that converts fibrinogen to fibrin and is generated through a series of proteolytic enzymatic reactions known as the coagulation cascade

202
Q

What clotting components are in the subendothelial collagen?

A

Collagen, and tissue factor - a transmembrane protein found within adventitia of blood vessels, monocytes and other tissues

203
Q

WHat occurs when blood vessel wall is injured?

A

Collagen and tissue factor are exposed to the blood

Collagen binds von willebrand factor

204
Q

What occurs after vWf binds to collagen in cell wall injury?

A

Platelets aggregate (adhesion) and release their granule contents

This allows for aggregation of platelets

205
Q

What is the primary hemostatic plug in vessel injury?

A

Platelet aggregation, which is then covered by fibrin

206
Q

What initiates the coagulation pathway?

A

Exposure of tissue factor at site of vessel injury and on surface of platelets

207
Q

What happens when Tissue factor binds to factor VII (VIIa)?

A

More VIIa is activated, which mediates activation of factor X (X to Xa) via serine protease activity

Xa activates prothrombin to thrombin (II to IIa)

Thrombin activates lots of stuff

208
Q

What does thrombin activate?

A

platelets, V, VIII, XI and XIII

209
Q

What occurs during hte amplificaiton phase of coagulation?

A

Tissue factor and VIIa activate IX to IXa

Forms tenase complex when combined with VIIIa to activate X to Xa

210
Q

What is teh “common pathway” of coagulation?

A

From X-Xa down

211
Q

What is the Boost phase of coagulation?

A

Thrombin activates XI to XIa, which activates IX to IXa

Drives more fibrin formation

212
Q

What is released when fibrinogen is cleaved by thormbin to fibrin monomers?

A

Fibrinopeptide A and B - can tell us that coagulation is occuring

213
Q

What occurs after thrombin acts on fibrinogen to produce fibrin monomers?

A

Factor XIIIa mediates cross-linked fibrin polymer clot formation

214
Q

How do you assess hemostasis clinically?

A

History - site of bleedign, kind of bleeding, inciting event; family hx; meds; other medical problems

Physical exam

Peripheral blodo smear - platelets; RBC changes (schistocytes - DIC: target cells - liver disease; burr cells - renal disease)

215
Q

What is this?

A

Senile purpura

216
Q

What is this?

A

Echymosis

217
Q

WHat is this?

A

Hemoarthrosis

218
Q

What is this?

A

Petechiae

219
Q

What are coagulation tests?

A

Prothrombin time

Partial thromboplastin time

Thrombin time

Mixing studies

Clotting factor assays

Fibrinogen level

Fibrin degradation prodcuts

D-Dimer

Bleedign time

Platelet aggregation studies

220
Q

What is prothrombin time?

A

Plasma + calcium + phospholipid + tissue factor

221
Q

How is prothrombin time reported?

A

INR (International normalized ratio)

222
Q

What is partial thromoplastin time?

A

Plasma + calcium + phospholipid + “surface”

Differs from prothrombin time in that it uses surface instead of tissue factor

223
Q

What is thromin time?

A

Plasma + thrombin

224
Q

What are the differences between what prothrombin time, partial thromboplastin time and thromibn time measure?

A
225
Q

WHat lab test measures the “contact” pathway?

A

Partial thromboplatin time

226
Q

What lab test measures the internal pathway of coagulation?

A

Prothrombin time - uses tissue factor

227
Q

What are the major acquired disorders of coagulation?

A

Impaired coagulation factor synthesis (Vit. K def.; Liver disease; Warfarin anticoagulants)

Consumption (or loss) of factors (DIC; Massive transfusion; nephrotic syndrome)

Inhibitors of coagulation (Factor inhibitors; antiphospholipid antibodies)

228
Q

What is classic hemophilia?

A

Hemophilia A

X-linked recessive disorder; 30% are sporadic though

Decreased or absent factor VIII coagulant activity

229
Q

What disease is caused by decreased or absent factor VIII coagulant activity?

A

Hemophilia A (classic hemophilia)

230
Q

What is hemophilia A?

A

Classic hemophilia

X-linked recessive; can be sporadic though

Absent or decreased factor VIII coagulant activity

231
Q

What are symptoms of Hemophilia A?

A

Bleeding (joints, muscles, GU, GI, CNS, post dental

Correlates with factor levels (lower the worse)

Complications include chronic arthropathy, narcotic addictions, transfusion transmitted disease, and inhibitor (antibody) formation

232
Q

What are lab findings in hemophilia A

A

Prolonged PTT with normal PT

Decreased FVIII levels

Can do gene mutation analysis

233
Q

How do you treate hemophilia A?

A

Recombinant FVIII (expensive!)

Desmopressin - stimulates secretion of vWF and VIII from endothelial cells

For inhibitors - FEIBA (factor eight inhibitor bypassing activity), recombinant FVIIa, immunosuppression

234
Q

What is Hemophilia B (Christmas Disease)?

A

Looks exactly like Hemophilia A, but is caused by a deficiency of factor IX

235
Q

What disease is caused by deficeincy of factor IX?

A

Hemophilia B

236
Q

What is Hemophilia C?

A

Factor XI deficiency

Autosomal recessive (9% of Ashkenazi jews are carriers)

Prolonged PTT, Normal PT, decreased XI

Variable bleeding

237
Q

What disease is caused by factor XI deficiency?

A

Hemophilia C

238
Q

What are deficiencies of XII, HMWK, Prekallikrein associated with?

A

NOT associated with bleeding

239
Q

What is the most common inherited bleedign disorder?

A

Von Willebrand Disease

240
Q

What is Von Willebrand Disease?

A

Autosomal dominant

Mucocutaneaous bleeding

Prolonged “bleeding time”, usually low VWF levels

Prolonged PTT (VWF is carrier molecule for VIII)

Treat with DDAVP (releases VWF from endothelial cells)

241
Q

What is prothrombin time in Von Willebrand Disease?

A

Normal

PTT is prolonged

Bleedign time is prolonged

242
Q

What is the Partial Thromboplastin time (PTT) in Von Willebrand Disease?

A

Prolonged

243
Q

What is “bleeding time”?

A

Measures ability of platelets to adhere and form small clot at cut in forearm - quantitative measurement of platelet adhesion issue

Platelet disfunction (Von Willebrand Disease; NSAIDS, aspirin,…) or Low platelet number will increase this

244
Q

How does Vitamin K deficiency cause disorder of coagulation?

A

Causes impaired production of II, VII, IX, X (both pathways affected)

Pts have prolonged PT, PTT times, and correction with mixing.

245
Q

How do you get vitamin K deficiency?

A

Poor nutrition (found in leafy plants and oils)

Poor absorption or biliary obstruction (fat soluble)

Antibiotics can deplete intestinal bacteria that make Vit. K

246
Q

Why can you get bleeding in liver disease?

A

Factor deficiencies (all made in liver)

Biliary obstruction can impair vit. K absorption

Consumption of clotting facotr

Thrombocytopenia secondary to hypersplenism

Prolonged PT, PTT, hypofibrinogenemia

247
Q

What is DIC??

A

Disseminated Intravascular Coagulation - Consumptive Coagulopathy

Activation of clotting throughout vascular tree with dissemminated fibrin deposition resulting in consumption of clotting factors and platelets

Always secondary to tissue injury that releases tissue factor or endothelial injury that exposes collagen

Clinical: Diffuse bleeding, purpura, petichiae; microvascular thrombi; microangiogpathic hemolytic anemia

Labs: Prolonged PT, PTT, decreased fibrinogen, elevated fibrin degradation products, elevated D dimer

Treat underlying cause

248
Q

What are clinical features of DIC?

A

Diffuse bleedign, purpura, petechiae

Microvascular thrombi (ischemia, gangrene)

Microangiopathic hemolytic anemia

249
Q

What will labs be for patient with DIC?

A

Prolonged PT, PTT

Decreased fibrinogen, elevated fibrin degradation products, elevated D Dimer

250
Q

What are platelet disorders?

A

Too few (thrombocytopenia)

Too many (Thrombocytosis)

Dysfunctional

251
Q

Why do you look at peripheral blood smear in low platelet count patients?

A

Pseudothrombocytopenia - secondary to platelet clumping from EDTA-associated agllutinins

252
Q

What is pseudothrombocytopenia?

A

Secnodary to platelet clumping from EDTA-associated agglutinins

May give falsely decreased platelet count

253
Q

What is this?

A

Pseudothrombocytopenia

254
Q

What is immune thrombocytopenia?

A

Autoantibodies to platelets - removed from circulation by reticuloendothelial system

INcreased megas in BM

large platelets on blood smear

255
Q

How do you treat immune thrombocytopenia?

A

Steroids, IVGG

Splenectomy

Win-RHo (anti-D antibody)

Rituximab

256
Q

What is the most common medication-mediated thrombocytopenia?

A

Heparin associated thrombocytopenia

Occurs 4-14 days post exposure

Antibodies to heparin complexed with platelet factor 4

Paradoxiacl arterial or venous thrombosis secondary to action of antibodies on endothelial cells and activation of platelets

STOP HEPARIN IMMEDIATELY and give non-heparin anticoagulation

257
Q

What do you do with patients wiht heparin associated thrombocytopenia?

A

STOP HEPARIN IMMEDIATELY and give other anti-coagulant

258
Q

Why do you get thrombosis in heparin associated thrombocytopenia?

A

Secondary to action of antibodies on endothelial cells and activation of platelets

259
Q

What is thrombocytosis?

A

Increased number of platelets

Primary - myeloproliferative diseases, thrombosis and bleeding risk

Reactive - infection, malignancy, iron deficiency, bleeding

260
Q

What are acquired qualitative disorders of platelets?

A

Aspirin - irreversibly blocks COX-1 and interferes with platelet thromboxane production

NSAIDs - reversibly inhibit COX and COX-2 inhibitors decrease prostacyclin; it inhibits platelet function, the reduciton of PGI by COX-2 inhibitors may explain increased cardiovascular risk (activated platelets)

Uremia - accumulation of toxic metabolites interfere with platelet function

Myeloproliferative disorders

261
Q

What are inherited qualitative disorders of platelets?

A

Von Willebrand Disease - most common inherited bleedign disorder; mucocutaneous bleeding, increaed bleedign time, PTT

Glanzmann Thrombasthenia - abnromal αΙΙbβ3 (platelet fibrinogen receptor; impaired aggregation); mucocutaneous bleeding

Bernard Soulier Syndrome - abnormality of GPIb, impaired adhesion

262
Q

What factors regulate clotting?

A

intact endothelium

Normal blood flow (stasis, turbulent flow, etc.)

Destruction of fibrin clot (fibrinolysis)

Elimination of activated clotting factors (removal by liver, inactivation by antithrombin, protein C, protein S or tissue factor pathwya inhibitor)

263
Q

What is the effect of Nitric oxide on clotting?

A

vasodilator, inhibitor of platelet aggregation

264
Q

What is the effect of prostacyclin on clotting?

A

vasodilation, inhibits platelet aggregation

265
Q

What is the effect of thrombomodulin on clotting?

A

receptor for thrombin, complex activates protein C which inhibits VIIIa and Va

266
Q

What is the effect of tissue factor pathway inhibitor on clotting?

A

Inactivates VIIa and Xa

Produced by endothelial cells

267
Q

What is fibrinolysis?

A

Enzymatic destruciton of fibrin clot by plasmin

268
Q

What controls fibrinolysis? Why?

A

Things can dampen fibrin clot so that you can actually clot when you need to

α2 antiplasmin acts on plasmin and plasminogen activator inhibitor 1 acts on tissue plasminogen activator

269
Q

How does elimination of activated clotting factors regulate clotting?

A

Removal by liver

Inactivation by endogenous anti-coagulant systems (protein C, Protein S, antithrombin III and tissue factor pathway inhibitor)

270
Q

What is the protein C protein S system?

A

Vitamin K dependent factors made in the liver

Protein C is activated by thrombin bound to its endothelial receptor, thrombomodulin

Activated protein c (APC) along with protein S, inhibits Va and VIIIa

Part of the endogenous anti-coagulant system

271
Q

WHat is antithrombin III?

A

Serine protease inhibitor (serpin)

made in liver

Complexes with serine proteases and inactivates them (XIIa, XIa, Xa, IXa, and thrombin)

Binds to heparan sulfate on endothelial cells which undergoes conformational change which potentiates ATIIIs ability to inactivate thrombin

This is how exogenous heparin works

272
Q

How does exogenous heparin work?

A

Binds antithrombin and mediates inactivaiton of clotting factors

273
Q

What is tissue factor pathway inhibitor?

A

Made by endothelial cells

Circulates in plasma and inactivates Xa and tissue factor/VIIa complex

Heparin stimulates release of TFPI, potentiating its anticoagulant effect

274
Q

HOw does protein C protein S system work?

A
275
Q

HOw does antithrombin III work?

A
276
Q

How does TFPI work?

A
277
Q

When does thrombosis occur?

A

Breakdown in balance between thrombogenic factors and protective mechanisms

278
Q

What are thrombogenic factors?

A

Virchow’s Triad

Vessel wall damage

Static or turbulent flow

Coagulable state of blood (hypercoagulability) - activation of platelets/clotting

279
Q

What is Virchow’s Triad??

A

Vessel wall damage

Static or turbulent flow

Coagulable state of blood (hypercoagulability) - activation of platelets/clotting

280
Q

What is hypercoagulability?

A

Acquired and inherited conditions resulting in increased tendency to develop thrombosis

281
Q

What is thrombophilia?

A

Inherited tendency to develop thrombosis

282
Q

When do you see thrombophilia?

A

Younger individuals (<50 years old) where you see venous thromboemobolism in abnormal places or arterial thrombosis (ATIII deficiency)

Acquired risk factors further increase incicdence of thrombosis in these patients

283
Q

What is the most common thrombophilic disorder?

A

Factor V Leiden mutation

284
Q

What is Factor V Leiden mutation?

A

Most common mutation in patients wtih venous thrombosis

Mutated factor V is resistant to inactivation by activated protein C

Provided survival advantage when bleedign was a risk (not so great now)

285
Q

What is prothrombin gene mutation (G202010A)?

A

Results in 20% increase in amount of prothrombin in blood

Cause of thrombosis in 20-30% of individuals

Thrombophilia disease

286
Q

What is protein C and protein S deficiency?

A

Autosomal dominant thrombophilia disease

Impaired inactivation of Va and VIIIa

Homozygous is incompatible with life

Hets have 3x risk of thromboembolism

287
Q

What is Warfarin Skin necrosis?

A

In patients with protein C or S deficiency - thrombosis of vessels in subcutaneous fat in these patients that receive anti-coagulation with warfarin

Common in abdominal vessels

288
Q

What is antithrombin III deficiency?

A

Rare, autosomal dominant thrombophilia

Quantitative and qualitative defects in ATIII

Ineffective inhibition of XIIa, XIa, Xa, IXa and thrombin (increased venous thromboembolism)

One mutation predisposes to areterial thrombosis

289
Q

What is inherited hyperhomocysteinemia?

A

Enzyme deficiencies lead to elevated homocystine

Increased risk of arterial and venous thromboembolism

Unclear mechanism

290
Q

What are some acquired risk factors for hypercoagulability?

A

Preganancy

Immobilization

Malignancy

Obesity

Birth control pills

Acquired ATIII deficiency (liver disease, nephrotic syndrome)

Blood disease

Heparin induced thrombocytopenia

Antiphospholipid syndromes

291
Q

What blood issue do you suspect here?

A

DVT

292
Q

What is antiphospholipid syndrome??

A

Antibodies that attach phospholipids

Interfere with negatively charged phospholipid used in clotting assays, so they will paradoxically present with a prolonged aPTT

Seen in collagen vascular disease, liver disease, malignancies and normal people

Associated iwth venous and arterial thrombosis

Mixing studies with no correction!

293
Q

What is the most common cause of drug-induced thrombocytopenia?

A

Heparin

Antibodies to heparin are complexed with platelet factor 4

Paradoxical arterial or venous thrombosis secondary to action of antibodies on endothelial cells and activation of platelets

Tx by STOPPING HEPARIN IMMEDIATELY, and putting them on anticoagulation (non-heparin)

294
Q

What is a concern with warfarin in pregnant women?

A

Teratogenic

295
Q

What is the defect in Glanzmann Thrombasthenia?

A

Abnormal GPIIb/IIIa - decreased fibrinogen binding, absent platelet aggregation, abnormal clot retraction, decreased platelet fibrinogen

296
Q

What is a unifying characteristic of all of the hematologic malignancies?

A

They are all clonal - all arose from a single cell

297
Q

What are the myeloproliferative disorders?

A

Chronic Myelogenous Leukemia

Polycythemia Vera

Essential Thrombocytothemia

Agnogenic Myeloid Metaplasia (Myelofibrosis)

298
Q

What define the acute leukemias?

A

Clonal, stem cell disorders

Impaired differentiation of hematopoietic cells resulting in block of their development into mature, functioning blood cells

Marrow replaced by immature leukemic blasts

Can’t differentiate between the different acute leukemias, just that it IS an acute leukemia

299
Q

What is Acute Myelogenous Leukemia (AML)?

A

Rare

Median age at diagnosis = 65-70

Risk factors are Benzene, ionizing radiation, chemo

300
Q

How do you diagnose/classify acute leukemias?

A

Cytochemistry (used less now)

Immunophenotype - flow cytometry with CD antigens

Cytogenetics

Molecular analysis (FISH, PCR)

301
Q

What are features of acute leukemia on bone marrow aspirate?

A

Hypercellularity, blastic - high nuclear to cytoplasmic ratio

AML can be identified by Auer Rods

302
Q

What are Auer Rods?

A

Accumulation of granules seen in AML only

303
Q

What is this?

A

Burkitt’s Leukemia

304
Q

What are clinical features of acute leukemia?

A

Leukocytosis:

50% normal or low WBC
Neutropenia

Hyperleukocytosis (> 50,000)

Anemia

Thrombocytopenia

Coagulopathy

Organ Infiltration

305
Q

What are complications seen in acute leukemia?

A

Infection secondary to neutropenia (bacterial, fungal, viral)

Bleeding

Hyperleukocytosis - in CNS and lungs

Extramedullary inflitration - gingival hyperplasia, CNS

306
Q

How do you treat acute leukemias?

A

Supportive care (hydration, allopurinol, antibiotics, transfusions, growth factors)

Induction chemotherapy (7+3, ATRA)

Post remission therapy

307
Q

What is a different between MDS and MPS?

A

MPS - full maturation of all cell lineages

MPS - extramedullary hematopoiesis

308
Q

What is a unique feature of myeloproliferative neoplasms?

A

You see extramedullary hematopoiesis

309
Q

Is development of marrow fibrosis a unique feature of myeloproliferative neoplasms?

A

NOPE - but it is seen

310
Q

What are the philadelphia chromosome-positive myeloproliferative neoplasms?

A

Chronic myelogenous leukemia

311
Q

What are the philadelphia chromosome neagitve myeloproliferative neoplasms?

A

Polycythemia rubra vera

Essential thromobcythemia

Primary myelofibrosis

Chronic eosinophilic leukemia

Chronic neutrophilic leukemia

Systemic Mast Cell

312
Q

What is the basis chronic myelogenous leukemia?

A

t(9;22)

BCR-ABL fusion protein has constitutive tyrosine kinase activity

Resistance to apoptosis

313
Q

What can increase the risk of CML?

A

Ionizing radiation exposure, benzene exposure, etc

314
Q

What are clinical features of CML?

A

Fatigue, fevers, sweats, bone pain (most are asymptomatic, though)

Splenomegaly - extramedullary hematopoiesis

Granulocytosis, Thrombocytosis, Basophilia, Anemia

315
Q

How do you diagnose CML?

A

Cytogeneitc - Philadelphia chromosome

FISH - for BCR-ABL = this is not specific, though ! ALL!

316
Q

How do you track the course fo treatment in CLL?

A

BCR-ABL PCR levels

317
Q

How do you treat CLL?

A

Irradiation, chemo, Stem cell transplant

TYROSINE KINASE INHIBITORS - imatinib, dasatinib, nilotinib (Gleevec)

318
Q

What are features of polycythemia vera?

A

Elevated hemoglobin/hematocrit

White count, red count, platelets too

Spurious due to decreased plasma volume

True due to increase in red cell mass (primary or secondary)

319
Q

What can cause primary polycythemia?

A

(in the setting of low EPO levels)

Polycythemia vera

Activating mutations of EPO receptor

Chuvash polycythemia

Idiopathic familial polycythemia

320
Q

What is the first lab test you perform when you identify a patient with polycythemia?

A

EPO levels - high or low? primary or secondary?

321
Q

Who gets polycythemia vera?

A

Median age 60

men more than women

322
Q

What are clinical features of polycythemia vera?

A

Plethora - redness in face

Headache, weakness, diziness

Pruritis (after showering)

Gout (hyperuricemia)

Venous and arterial thrombosis - Budd Chiari (hepatic vein thrombosis)

Bleeding

323
Q

What is the MCV of patients in polycythemia vera?

A

Low - iron deficiency

324
Q

How is Polycythemia Vera diagnosed?

A

Low EPO levels

Bone marrow aspirate and biopsy

Cyotgenetic and molecular studies

325
Q

What is the molecular basis for polycythemia vera?

A

Mutated JAK-2 in cells

Disrups normal inhibitory regulation of JAK2 - results in constituitive activity in absence of hematopoetic growth factors

May confer proliferative and survival advantage (EPO/TPO independence)

326
Q

What are complications of polycythemia vera?

A

Thrombosis (Budd-Chiari)

Increased blood viscosity

Qualitative and quantitative platelet defects

Bleeding

Transforming to stent phase

Transforming to AML

Solid tuomrs

327
Q

How do you treat polycythemia vera?

A

Phlebotomy (Hct <45%)

Myelosuppression (hydroxyurea, anagrelide, chlorambucil, 32Phosphorous)

Antiplatelet agents

328
Q

Who gets essential thrombocythemia?

A

females (2:1)

Median age at 60

Near normal life expectancy

329
Q

What is the pathogenesis of essential thromobcytothemia?

A

Clonal

TPO independence

Decreased c-MPL expression

JAK2 mutations in 50%

330
Q

How do essential thrombocythemia patients present?

A

Thrombocytosis (often > 1 million)

Splenomegaly
Thrombosis

Bleeding

Transformation to myelofibrosis, Polycythemia vera

Transformation to AML

331
Q

Where does essential thormobcythemia bleeding present?

A

Skin, mucous membranes, GI tract

Platelets are > 1 million

Use aspirin, NSAIDs

Can have acquired von Willebrand Disease

332
Q

How do you treat essential thromobcythemia?

A

Vasomotor symptoms/microvascular thrombi - low dose aspirin

Bleeding - avoid NSAIDS and ASA > 325 mg

High risk for thrombosis - Hydroxyurea

333
Q

What is an important mainstay of treatment of essential thromobcythemia?

A

Aspirin and Hydroxyurea

334
Q

What is primary myelofibrosis?

A

Clonal disease

Progressive marrow fibrosis

Extramedullary hematopoiesis

Cytosis, initially followed by cytopenias

Jak2 mutation in 50%

Leukemic transformation in 10-20%

335
Q

What do you see on blood smear of primary myelofibrosis?

A

Tear drops, leukoerythroblastosis

336
Q

What do you see in bone marrow of primary myelofibrosis?

A

Fibrosis - increased reticulin fibrosis

337
Q

How do you treat primary myelofibrosis?

A

Supportive - EPO, transfusions, splenectomy

Thalidomide (anti-angiogenic, anti-TNFα)

Etanercept (TNFα receptor)

JAK2 inhibitor (Ruxolitinib)

Allogenic stem cell transplantation

Hematology (1 decks)

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