Pathology Winter L4 Bleeding Disorder

Front 1

What is the normal percentages of Hematocrit and plasma?

Back 1

H= 45%
P=55%

Front 2

What are the percentages of hematocrit and plasma in secondary erythrocytosis?

Back 2

Hematocrit 56% (greatly increased RBC size)
Plasma 44%

but over all blood volume does NOT change here

Front 3

What are the percentages of hematocrit and plasma in Polycythemia vera?

Back 3

Hematocrit 52% (increased RBC size)
Plasma 48% also increased in volume

this has bigger RBC's and more blood volume total

Front 4

What are the percentages of hematocrit and plasma in Relative polycythemia?

Back 4

hematocrit is 52% but RBC's are normal size

Plasma is 48% but decreased in total volume

Front 5

What typically causes relative polycythemia, and what does the blood composition look like?

Back 5

this is caused by dehydration. you lose plasma volume, RBC's stay the same size as always, but now appear to be larger relative to the smaller plasma volume

Front 6

What are some of the causative agents of dehydration in relative polycythemia?

Back 6

diuretics
sweating
hanta virus
Stress** called gaisbock syndrome

Front 7

What causes polycythemia vera genetically?

Back 7

clonal proliferation of myeloid stem cells due to JAK2 mutation***

Front 8

What are erythropoietin levels like in polycythemia vera ?

Back 8

LOW erythropoietin (note the difference between this and absolute polycythemia, which is secondary)

Front 9

What causes absolute polycythemia (aka secondary)?

Back 9

this is caused by chronic hypoxia, due to CHF, high altitude living, pulmonary disease

Front 10

what are erythropoietin levels like in absolute polycythemia?

Back 10

these will be increased to an appropriate level based upon need

Front 11

When describing polycythemias, what does primary mean?

Back 11

this means EPO is low

Front 12

when describing polycythemias, what does secondary mean?

Back 12

this means EPO is high

Front 13

What causes absolute polycythemia, secondary- but due to inappropriate levels of EPO?

Back 13

renal cell carcinoma, and other cancers with paraneoplastic syndromes

Front 14

What are the three tests used for bleeding disorders?

Back 14

PT, PTT, Platelet count

Front 15

What factors are involved in the intrinsic pathway? what test measures this?

Back 15

XII, XI, IX, VIII

measured by aPPT.
more factors involved has more letters in the test name

Front 16

What factors are involved in the extrinsic pathway? what test measures this/

Back 16

TF, and VII

measured by PT

Front 17

What is the common pathway?

Back 17

X, V, II, I

Front 18

What pathway is defective in most hereditary bleeding disorders?

Back 18

this is most common in the intrinsic pathway

Front 19

What causes subungual hemorrhage?

Back 19

bacterial endocarditis, either subacute or actue

Front 20

What are the signs of infective endocarditis?

Back 20

crops of petechiae distributed throughout the skin, and under finger nails

Front 21

What causes Henoch- Schonlein purpura?

Back 21

this is a systemic hypersensitivity vasculitis reaction to an unknown antigen.

Circulating IgA*** deposits in vessel walls

Front 22

What is the presentation of henoch schonlein purpura?

Back 22

symptoms occur following a URI
-pupuric rash
-colicky pain
- polyarthralgia**
-acute glomerulonephritis (Tx fluids)

Front 23

What are some of the signs of Vitamin C deficiency?

Back 23

purpuric macular eruption associated with hair follicles
Corkscrew hairs
Bleeding gums
occult blood

Front 24

What is Ehlers-Danlos syndrome

Back 24

this is an inherited defect of collagen type 1 and 3.
leads to poor vascular support and easy bruising (and aortic aneurisms and stuff)

Front 25

What causes Batemen/actinic purpura?

Back 25

being old and having collagenous atrophy

Front 26

What is Osler-Weber-Rendu disease?

Back 26

this is hereditary hemorrhagic telangiectasia

Front 27

What are the clinical signs of Osler-Weber-Rendu disease?

Back 27

Tortous thin walled vessels in MOUTH, and under NAILS

Mucosal bleeds, nose bleeds, GI bleeds

Front 28

What is a major concern with Osler-Weber-Rendu disease?

Back 28

Arteriovenous malformations in the Brain, lung, and liver

Front 29

What is the other named for hereditary hemorrhagic telangiectasia?

Back 29

Osler-Weber-Rendu disease

Front 30

How is Osler-Weber-Rendu disease transmitted?

Back 30

this is autosomal dominant. look for strong familial correlation

Front 31

What type of amyloid is usually associated with systemic amylodiosis?

Back 31

AL- comes from monoclonal plasma cells, or multiple myeloma

Front 32

What type of amyloid is associated with cerebral amyloid angiopathy?

Back 32

A-beta (AB) amyloid

These depositions cause fragility and easy bleeding in these vessels

Front 33

Is cerebral amyloid angiopathy associated with alzhemiers?

Back 33

while it has the same amyloid type AB, it can occur with or without alzheimers

Front 34

What is the cut off number for thrombocytopenia?

Back 34

less than 150,000/mm3

Front 35

At what platelet count will people bleed spontaneously?

Back 35

less than 30,000/mm3

Front 36

at what platelet count range will people have a high risk of post traumatic bleeding?

Back 36

30,000-50,000/mm3

Front 37

What happens to PT and PTT with platelet dysfunctions?

Back 37

these will be normal!!***

Front 38

What are the clinical manifestations of thrombocytopenia?

Back 38

petechiae, ecchymoses, purpura, mucosal bleeding in many places

Front 39

What are the four main causes of thrombocytopenia

Back 39

decreased production
decreased survival
sequestration (splenomegaly)
dilution (transfusions)

Front 40

How does hypersplenism affect platelets?

Back 40

there is increased sequestration of platelets (up to 90% of bodies platelets) with splenomegaly of any cause

Front 41

What drugs can cause decreased platelet production?

Back 41

Alcohol, an thiazides

Front 42

What types of infections cause a reduction in platelets? how?

Back 42

HIV can infect marrow megakaryoctyes (which make platelets)
this lowers platelet counts

Front 43

What types of things cause pancytopenia? (three)

Back 43

-bone marrow tumors (myelophthisic)
-Ineffective megakaryopoiesis
-drug induced

Front 44

What kinds of drugs can cause aplastic anemia/pancytopenia?

Back 44

chemotherapy and alcohol

Front 45

What were the main causes of decreased platelet survival- mechanical?

Back 45

narrow vessels (due to HTN, or Microangiopathic hemolytic anemia)

Prosthetic heart valves

Front 46

What are the immunologic causes of decreased platelet survival?

Back 46

Antiplatelet antibodies

Circulating immune complexes- ends up using up platelets where these deposit.

Sepsis- can lead to use of platelets on a grand scale

Front 47

What causes neonatal thrombocytopenia?

Back 47

maternal antibodies form against HPA inherited from the father.

this causes immune mediated platelet destruction

Front 48

What causes idiopathic thrombocytopenic purpura?

Back 48

autoimmune IgG antibodes attack common epitopes on platelet GP's

UNKNOWN CAUSE

Front 49

How are platelets destroyed in idiopathic thrombocytopenic purpura?

Back 49

IgG binds to platelet GP's, which are then opsonized and destroyed in the spleen

Front 50

What are the signs of ITP?

Back 50

petechiae
NORMAL SPLEEN SIZE
increased megakaroctyes
large thrombocytopenia (the platelets are large..think of it like RBC production, early RBC's are big too)

Front 51

Who usually gets chronic ITP?

Back 51

adult females under 40,

Front 52

What is the common clinical presentation of acute ITP?

Back 52

childhood, abrupt onset 2 weeks after a viral illness
Increased megakaryoctyes in the bone (means its not an aplastic type)

Front 53

What is the treatment for acute ITP?

Back 53

IVIG, steroids for severe thrombocytopenia

Front 54

What are the lab findings in ITP?

Back 54

PT, PTT are normal
low platelets
increased megakaryocytes
positive antiplatelet antibodies

Front 55

What type of heparin causes heparin induced thrombocytopenia?

Back 55

unfractionated heparin

Front 56

What the timing of type II HIT?

Back 56

onset 5-14 days after initial exposure.

large reduction (50%) of platelet count

Front 57

What is the root cause of type II HIT?

Back 57

antibodies to heparin-platelet factor 4 complex.

Front 58

What problems does HIT type II cause?

Back 58

antibodies activated heparin bound platelets. this leads to thrombi

these thrombi not only block stuff up, but also take away platelets from other places.

Makes you clot up and bleed. double bummer

Front 59

What is the most common hematologic abnormality in HIV?

Back 59

HIV associated thrombocytopenia

Front 60

What is the mechanism of HIV associated thrombocytopenia?

Back 60

HIV infects megakaryocytes
increased destruction due to immune dysregulation

Front 61

What are the three shared clinical features of Thrombotic thrombocytopenic purpura and Hemolytic uremic syndrome?

Back 61

Thrombocytopenia

intravascular thrombi

microangiopathic hemolysis

Front 62

What is the common pathogenesis of TTP and HUS?

Back 62

endothelial injury leads to vWF complex/platelet aggregation.

this causes thrombocytopenia

BUT- the vWF complex/platelet aggregations lead to microvascular thrombi (hyaline thrombi)

these little blockages cause mechanical lysis of RBC

Front 63

What is the seen in a peripheral blood smear with microangiopathic hemolytic anemia?

Back 63

schistocytes, helmet cells, triangulocytes

Front 64

What are TTP patients deficient that causes them to get TTP?

Back 64

these people are deficient in a protease ADAMTS 13, which breaks down vWF

this causes large vWF strands, leading to thrombi

Front 65

What are the five classic symptoms of TTP? what is the mnemonic?

Back 65

Fever
Anemia (microangiopathic)
Renal failure
Thrombocytopenia
'
Neurological defects (transient)

FART'N mnemonic

Front 66

What usually gets hemolytic uremic synrome?

Back 66

children and the elderly

Front 67

What are the signs of hemolytic uremic syndrome?

Back 67

these are the same as TTP, EXCEPT- no neuro defects

Front 68

What bug causes hemolytic uremic syndrome?

Back 68

E. Coli O157:H7

Front 69

What is the clinical progression of HUS?

Back 69

bloody diarrhea of acute gastroenteritis followed by renal failure a few days later

(caused by shiga toxin entering blood)

Front 70

What are hyaline thrombi? what diseases have them?

Back 70

these are platelet aggregates that come together and form hyaline thrombi

this is found in TTP, HUS, and microangiopathic hemolytic anemias

Front 71

What is the treatment for HUS?

Back 71

NO antibiotics***
just supportive care

Front 72

How does liver disease cause acquired bleeding disorder?

Back 72

this fails to manufacture the procoagulants

Front 73

What does Vitamin K deficiency cause?

Back 73

this causes an acquired bleeding disorder- leads to deficiencies of VII, IX, X, II, protein C

Front 74

What does Factor VIII do?

Back 74

this is a cofactor of IX, which together activate X

Front 75

Where is Factor VIII produced?

Back 75

In the liver

Front 76

What is the defect in X linked Hemophilia A?

Back 76

this is a Factor VIII deficiency

Front 77

What does vWF do to VIII?

Back 77

this stabilizes VIII and extends its life time.

Front 78

What is the inheritance of vWF disease?

Back 78

autosomal dominant

Front 79

How does vWF help bind platelets? to what?

Back 79

this binds platelets to the endothelium when exposed. it interacts with glycoprotein 1b-IX

Front 80

What is the clinical presentation of vWF disease?

Back 80

spontaneous mucosal bleeds,
excessive wound bleeds

NORMAL platelet count***
Prolonged Bleeding time***

Front 81

What is the inheritance and labs of type 1 vWF disease?

Back 81

autosomal dominant

decreased vWF and normal PTT

only has mild bleeding

Front 82

What is the inheritance and labs of type 2 vWF disease?

Back 82

inheritance not stated

this is due to a defect in the makeup of vWF, labs unknown

Front 83

What is the inheritance and labs of type 3 vWF disease?

Back 83

Autosomal recessive***


**prolonged PTT, hemarthosis (joint bleeds)

may present like factor VIII defect

Front 84

What is the treatment for vWF disease?

Back 84

desmopressin

cryoprecipitate (1unit/10kg bid)

Front 85

What are the clinical features of abnormal clotting factor bleeds?

Back 85

Large ecchymoses
hematomas
hemarthrosis (joint bleeding)
prolonged bleeding for DAYS after injury
GI bleeds
bleeds into weight bearing joints ***

Front 86

What element of the coagulation cascade is defective in a person with hemophilia A?

Back 86

Factor VIII

Front 87

What is the most common Serious hereditary bleeding disorder?

Back 87

Factor VIII deficiency hemophilia A

Front 88

What about factor VIII is affected in hemophilia A?

Back 88

this affects the level of activity* or failure of synthesis**

Front 89

How is Hemophilia A inherited?

Back 89

X linked recessive

Front 90

What causes the most serious type of Hemophilia A?

Back 90

a DNA inversion in the part that makes factor VIII

Front 91

What are the clinical features of hemophilia A?

Back 91

massive hemorrhage following trauma.
spontaneous hemorrhage
easy brusing
hemarthrosis with deformity
CNS hemorrhage

NO PETECHIAE***

Front 92

What lab vales are abnormal with factor VIII defect?

Back 92

PTT is prolonged

PTT pathway is XII-> XI-> IX-> VIII

Front 93

What is the Tx for hemophilia A?

Back 93

infusion of factor VIII concentrates

maybe factor eight inhibitor bypass agent

Front 94

What lab test is abnormal with hemophilia B?

Back 94

PTT is long

Front 95

What is hemophilia B a defect in?

Back 95

factor IX

Front 96

What is Christmas Disease?

Back 96

Hemophilia B

Front 97

How is hemophilia B inherited?

Back 97

X linked recessive

Front 98

What is the most common autosomal coagulation factor deficiency?

Back 98

factor XI deficiency

Front 99

What group of people has Factor XI deficiency

Back 99

Ashkenazi Jews

Front 100

What lab values are abnormal in Factor XI deficiency?

Back 100

PTT prolonged

Front 101

What are the two major causes of DIC?

Back 101

release of tissue factor or thromplastic substances into circulation

Sepsis**

Front 102

What is the most common cause of DIC?

Back 102

sepsis- most common.
septic shock/meningiococcemia

Front 103

How do obstetric accidents cause DIC?

Back 103

premature separation of placenta, amniotic fluid embolism, or retained dead fetus can all leak clot inducing materials into the maternal blood stream

Front 104

What organs are most affected by microthrombi in DIC?

Back 104

kidneys, adrenals, brain, and heart

Front 105

What is waterhouse-friderichsen syndrome?

Back 105

bilateral infarcts of the adrenals, hemorrhage, adrenal failure, and death

Front 106

How can you both clot up and bleed with DIC?

Back 106

the activated endothelium cases tons of small clots to form all over the place, but this ends up using up all the clotting factors/platelets.

So your clotted in some places, and bleeding everywhere else

Front 107

What is chronic DIC associated with?

Back 107

malignancy and recurrent DVT

Front 108

What is the Tx for DIC?

Back 108

give anticoagulant and procoagulant replacement, including platelets

Front 109

What labs will be HIGH in DIC?

Back 109

FDP and D dimer