Hematology Week 3

Front 1

This is a 30-year-old male who drank 6-8 bottles of beer daily, and had a history of dyspepsia for which he took Bromoseltzer. he went on an alcoholic binge, drinking 15 beers and blacked out 2 days prior to admission. The next day he developed melena followed by vomiting blood on the day of admission.
Past history revealed that he had required a 3-unit blood transfusion for blood loss form severe facial trauma and a 1-unit blood transfusion following a dental extraction.
On admission his pulse awas 140/min, BP 140/100 and PCV 35%. Liver function tests and amylase were normal. Endoscopy showed no esophagela varices but did show a diffuse hemorrhagic gastritis. He continued to bleed over the next two days, the PCV falling to 9%. A 10-unit blood transfusion brought his PCV to 26%. An emergency upper GI series was interpreted as showing a duodenal ulcer.

Labs:
PT: 12"
PTT: 60"
Thrombin time: 20"
Protamine: negative
Bleeding time: 4.5'
Platelets: 200,000/uL

Which of the following would most likely account for

Back 1

C. Hemophilia A or B

Normal PT means that factors VII, X, V, thrombin, and fibrin are okay, so it can't be Vitamin K, liver disease, or factor V deficiency.

Front 2

This is a 30-year-old male who drank 6-8 bottles of beer daily, and had a history of dyspepsia for which he took Bromoseltzer. he went on an alcoholic binge, drinking 15 beers and blacked out 2 days prior to admission. The next day he developed melena followed by vomiting blood on the day of admission.
Past history revealed that he had required a 3-unit blood transfusion for blood loss form severe facial trauma and a 1-unit blood transfusion following a dental extraction.
On admission his pulse awas 140/min, BP 140/100 and PCV 35%. Liver function tests and amylase were normal. Endoscopy showed no esophagela varices but did show a diffuse hemorrhagic gastritis. He continued to bleed over the next two days, the PCV falling to 9%. A 10-unit blood transfusion brought his PCV to 26%. An emergency upper GI series was interpreted as showing a duodenal ulcer.

Labs:
PT: 12"
PTT: 60"
Thrombin time: 20"
Protamine: negative
Bleeding time: 4.5'
Platelets: 200,000/uL

The next test that should be done on this patient is:

Back 2

A. 50/50 PTT

Front 3

This is a 30-year-old male who drank 6-8 bottles of beer daily, and had a history of dyspepsia for which he took Bromoseltzer. he went on an alcoholic binge, drinking 15 beers and blacked out 2 days prior to admission. The next day he developed melena followed by vomiting blood on the day of admission.
Past history revealed that he had required a 3-unit blood transfusion for blood loss form severe facial trauma and a 1-unit blood transfusion following a dental extraction.
On admission his pulse awas 140/min, BP 140/100 and PCV 35%. Liver function tests and amylase were normal. Endoscopy showed no esophagela varices but did show a diffuse hemorrhagic gastritis. He continued to bleed over the next two days, the PCV falling to 9%. A 10-unit blood transfusion brought his PCV to 26%. An emergency upper GI series was interpreted as showing a duodenal ulcer.

Labs:
PT: 12"
PTT: 60"
Thrombin time: 20"
Protamine: negative
Bleeding time: 4.5'
Platelets: 200,000/uL
50/50 PTT is normal

The next test that should be done

Back 3

A. Factor VIII assay

Hemophilia A is 3X as common as Hemophilia B.

Front 4

Case 2.

Laboratory data:
Hct: 46%
WBC: 17,400
Na: 145 meq/L
PT: >180"
Aspirin level: 4 mg%

She was given 15 mg Vitamin K IV at 6pm.

Hemostatic data:
PT: >180"
PTT: 212"
TT: 25"
Protamine: negative
Fibrinogen: 150 mg/dl
Factor V: 1.5%
Factor VII: 1%
Platelets: 175,000/uL
Bleeding time: 8 min.

The most likely reason for this abnormal hemostatic data is:
A. Vitamin K deficiency
B. DIC
C. Severe liver failure
D. Autoantibody to factor V

Back 4

C. Severe liver failure

Factors V and VII are synthesized in the liver, but Factor VII is not Vitamin K dependent. DIC is not likely because platelets were within normal limits and protamine was negative.

Front 5

Which of the following hemostatic studies should be done next?
A. Factor II level
B. 50/50 PT and PTT
C. Factor VIII level
D. Factor IX level

Back 5

B. 50/50 PT and PTT to rule out an inhibitor

Front 6

Which of the following laboratory studies should also be ordered?
A. Tests of liver function and injury
B. Vitamin K level
C. Tests of kidney function
D. Toxicology screen for illegal drugs

Back 6

A. Tests of liver function and injury

Front 7

This is a 20-year-old male post open heart surgery for a ventricular spetal defect. The patient continued to ooze post-operatively. A clotting screen was obtained three-hours post-operatively.
Labs:
PT: 14"
PTT: 58"
TT: >180"
Protamine: Weakly +
D-dimer: Minimally elevated
Fibrinogen: 300 mg/dl
Bleeding time: 25 min
Platelet count: 100,000/uL

Which of the following is the most likely cause of the abnormal coagulation test abnormalities?
A. Vitamin K deficiency
B. Pathologic fibrinolysis
C. Inhibitor of Factor VIII
D. Heparin

Back 7

D. Heparin

Patients on bypass are put on heparin. Infinite thrombin time indicates lack of fibrinogen or complete inhibition of thrombin (such as by heparin).

Front 8

This is a 20-year-old male post open heart surgery for a ventricular spetal defect. The patient continued to ooze post-operatively. A clotting screen was obtained three-hours post-operatively.
Labs:
PT: 14"
PTT: 58"
TT: >180"
Protamine: Weakly +
D-dimer: Minimally elevated
Fibrinogen: 300 mg/dl
Bleeding time: 25 min
Platelet count: 100,000/uL

What definitive test should be done next to establish the etiology of the abnormal coagulation studies?
A. Vitamin K level
B. Dilute whole blood clot lysis time
C. Factor VIII assay
D. Repeate thrombin time after protamine neutralization of heparin

Back 8

D. Repeat thrombin time

Front 9

This is a 20-year-old male post open heart surgery for a ventricular spetal defect. The patient continued to ooze post-operatively. A clotting screen was obtained three-hours post-operatively.
Labs:
PT: 14"
PTT: 58"
TT: >180"
Protamine: Weakly +
D-dimer: Minimally elevated
Fibrinogen: 300 mg/dl
Bleeding time: 25 min
Platelet count: 100,000/uL

Is the prolonged PTT, pro time, and thrombin time the only possible cause of the patient's bleeding?

Back 9

No, if heparin has been neutralized with protamine and the patient is still bleeding then there is either a systemic hemostatic defect or the surgeon fucked up.

Front 10

This is a 67 year old Caucasian male who was admitted with delirium tremens, multiple bruises and a PCV or 29% which fell to 17% one day later without evidence of external blood loss. PE showed a chronically ill man with large indurated bruises.

Hemostatic data:
PT: 12"
PTT: 80"
TT: 23"
Protamine: -
D-dimer: normal
BT: 6'
Platelets: 175,000/uL

Which of the following best explain the clinical and hemostatic data?
A. Liver failure
B. Vitamin K deficiency
C. Inhibitor of Factor VIII
D. Inhibitor of Factor V

Back 10

C. Inhibitor of Factor VIII

PT would be long in all other cases.

Front 11

This is a 67 year old Caucasian male who was admitted with delirium tremens, multiple bruises and a PCV or 29% which fell to 17% one day later without evidence of external blood loss. PE showed a chronically ill man with large indurated bruises.

Hemostatic data:
PT: 12"
PTT: 80"
TT: 23"
Protamine: -
D-dimer: normal
BT: 6'
Platelets: 175,000/uL

What test should be done next?
A. Hepatic tests of function and injury
B. Factor VII levels
C. 50/50 PTT
D. Factor V level

Back 11

C. 50/50 PTT

Front 12

This is a 67 year old Caucasian male who was admitted with delirium tremens, multiple bruises and a PCV or 29% which fell to 17% one day later without evidence of external blood loss. PE showed a chronically ill man with large indurated bruises.

Hemostatic data:
PT: 12"
PTT: 80"
TT: 23"
Protamine: -
D-dimer: normal
BT: 6'
Platelets: 175,000/uL

Which clotting factors could be defective in this case?
A. Factor VIII
B. Prekallikrein
C. HMWK
D. Factor II

Back 12

A. Factor VIII

Prekallikrein and HMWK can cause long PTT but not bleeding in the patient.

Front 13

This is a 37-year old Guatemalan male with a bleeding disorder manifested in childhood as bleeding for 2-3 days after loss of deciduous and permanent teeth. In 1950 following trauma, he developed a large hematoma of the right flank area that required 3-4 months to resolve. In 1967 he was shot in the chest with a resultant large hemothorax. Treated with several units of whole blood. Bleeding was not excessive and was promptly resolved. No Hx of bleeding into joints.

Hemostatic data:
PT: 12"
PTT: 30"
TT: 21"
Protamine: -
D-dimer: -
Fibrinogen: 300 mg/dl
Platelets: 250,000/uL
Bleeding time: 4 min.

Do you think that this patient has a significant bleeding disorder?

If yes, is this suggestive or a hereditary or acquired disorder?

Back 13

Yes, hereditary because it is lifelong.

Front 14

Which of the following disorders is most likely?
A. Mild hemophilia A or B
B. Factor XII deficiency
C. Abnormal fibrinogen
D. Factor XIII deficiency

Back 14

D. Factor XIII deficiency

Tests with Factor XIII deficiency are usually within normal limits, so you need to assay for Factor XIII.

Front 15

Case 6.
This is a 27-year-old female in the last month of pregnancy who suddenly developed severe lower abdominal pain. Shortly thereafter she went into labor with very severe contractions. On hospitalization the amniotic fluid was bloody and did not clot. Peripheral blood smear showed moderately reduced platelet count and Hgb was 6.5 g//dl. Here BP was low.
PT: >180"
PTT: >180"
TT: >180
Protamine: strongly +
D-dimer: >4000
Platelets: 75,000/uL

What is the most likely reason for the infinite coagulation tests?
A. No fibrinogen
B. No factor V
C. No factor VII
D. No factor IX

Back 15

A. No fibrinogen

Front 16

Which of the following statements is true?
A. Fragmented RBCs on peripheral blood smear
B. Fibrinogen level will be normal
C. Hgb level is not low enough to require RBC transfusion
D. EPO will be very low

Back 16

A. Fragmented RBCs may be present
(in about 50% of patients, some may clear the fragmented RBCs faster)

Front 17

This is a 58 year old Caucasian male with a lifelong bleeding disorder. Hx of many episodes of severe epistaxis requiring nasal packing and requiring transfusions on two occasions. Required transfusions following incision and drainage of an inguinal abscess. Suffered an esophageal laceration from swallowing a shrimp shell. That required 10 units of blood before hemostasis occurred. He had an episode of esophagitis also requiring a 10 unit blood transfusion for control of bleeding. Also had easy bruisability. Never had bleeding into joints or muscles.
Hemostatic data:
CBC: normal including platelets
PT: 12.5"
PTT: 50"
TT: 25"
Protamine: -
BT: 14'

The most likely cause of this man's bleeding disorder is:
A. Hemophilia A
B. Hemophilia B
C. Factor VII deficiency
D. von Willebrand's disease

Back 17

D. von Willebrand's disease

Front 18

All of the following tests should be done except:
A. Factor VIII assay
B. Ristocetin cofactor assay
C. vWF:Ag
D. Factor IX assay

Back 18

D. Factor IX assay

Factor VIII is carried by vWF. Ristocetin is related to vWF function, and of course you want to look for vWF:Ag.

Front 19

This patient has type I vWD.
He subsequently injures his knee and will require arthroscopic surgical repair. Which of the following therapies should be given prior to surgery to prevent bleeding?
A. Cryoprecipitate
B. Desmopressin acetate
C. Recombinant factor VIII concentrate
D. Fresh frozen plasma

Back 19

B. Desmopressin acetate

Desmopressin causes endothelial release of vWF. Cryoprecipitate could be used because it contains fibrinogen, factor VIII, factor XIII, and vWF, but 10 units would be required. Too much fresh frozen plasma would be required to be practical.

Front 20

This is a 47 year old woman with mitral valve disease secondary to rheumatic heart disease. She had a prosthetic valve replacement ans was currently on warfarin therapy to prevent clot formation and secondary arterial embolization. She had been stable on the same dose for many months. She had been doing well without new complaints. She had been placed on no new medicines and her warfarin dosage had not been changed. 3 days prior to this admission developed a headache and neck pain which worsened until admission. On PE she was lethargic and had nuchal rigidity. LP revealed bloody CSF.
Hemostatic data:
Hgb: 13
WBC: normal
Platelets: 250,000/uL
PT: 150"
PTT: 108"
50/50 PTT: 33"
TT: 28"
Protamine: -
D-dimer: -
The most likely cause of this woman's hemostatic abnormality is:
A. Autoantibody to Factor V
B. Inadvertent coumadin overdose
C. Liver failure
D. DIC

Back 20

B. Inadvertent coumadin overdose

Liver failure is possible, but hx is not compatible. Labs not compatible with autoantibody to factor V or DIC.

Front 21

You could treat this pt with all of the following except:
A. Fresh frozen plasma
B. IV vitamin K
C. IV Ig
D. Decadron to reduce cerebral edema

Back 21

C. IV Ig

IV vitamin K is the best option, but plasma could be used.

Front 22

This is a 48 year old man with known alcohol-induced liver cirrhosis, fell on a glass jar and sustained a deep laceration to his left forearm. Went to the ER wahere the would was sutured. 2 days after continued bleeding from laceration he returned to the ER where a bleeding vessel was ligated. Hct was 27%. 3 days later the laceration was stil bleeding, Hct 21%. Would was resutured and pressure dressing applied. 6 units packe dRBCs given. Denied previous bleeding history except esophageal varices. No family Hx of bleeding. Denied taking aspirin.
Hemostatic data:
Hgb: 7
WBC: 3,500 normal differential
Platelets: 75,000/uL
PT: 16"
50/50 PT: 12"
PTT: 78"
50/50 PTT: 34"
TT: 92"
50/50 TT: 30"
Protamine: -
D-dimer: -
Fibrinogen titer 0 hr: 1:128 (200 mg)
Fibrinogen titer 2 hr: 1:8 (50 mg)
Dilute whole blood clot lysis time: 1 hour (normal >4 hr)

Which of the following would not account for the clinical and lab data?
A. Splenomegaly
B. Decreased synthesis of coagulation factors byt he liver
C. Increased fibrinolysi

Back 22

D. Clotting factor inhibitor

Front 23

What is the probable reason for the patient's excessive bleeding from the laceration?
A. Thrombocytopenia
B. Decreased coagulation factors
C. Increased fibrinolysis

Back 23

C. Increased fibrinolysis

Decreased coagulation factors are probably contributory, but there is evidence of increased fibrinolysis. D-dimers may not be elevated if bleeding as a result of clot lysis all leaves the body.

Front 24

How would you best treat this patient?
A. Fresh frozen plasma
B. Platelet concentrates
C. Epsilon aminocaproic acid (AMICAR)
D. Desmopressin acetate

Back 24

C. AMICAR

AMICAR blocks fibrinolysis.

Front 25

A 29 year old newly married Caucasian woman is referred to you because of a hx of DVT of her left superficial femoral vein that occurred 3 months ago. She gave a hx of having started OCP for 3 months prior to the onset of thrombosis. At the time of her thrombosis, OCP were discontinued and she was treated with LMW heparin for 5 days and started on warfarin. During the past 3 months her PT INR was consistent between 2-3........

Heterozygote for factor V leiden by PCR. No evidence of prothrombin mutation. No other studies were done.

PE was normal except for swelling of the left leg. She and her husband would like to know whether any other studies should be done now and whether she could attempt to become pregnant now.

Which of the following tests should not be done at the present time?
A. Factor VIII coagulation level
B. Protein C and S activity levels
C. Antithrombin level
D. Plasma homocysteine level

Back 25

B. Protein C and S activity levels.

Nothing that she is taking would affect Factor VIII. Protein C and S are Vitamin K dependent and she is on coumadin, so this will be low. Antithrombin and plasma homocysteine levels are not affected by coumadin.

Front 26

Which of the following should you not advise?
A. Continue warfarin for 3 more months
B. Use non-hormonal contraception in the future
C. She could attempt to become pregnant in the next 3 months
D. She should be anticoagulated with heparin if she becomes pregnant

Back 26

C. She could attempt to become pregnant in the next 3 months

Continued anticoagulation therapy is advised because she still has clotting problems in her left leg. If she does become pregnant she should be anticoagulated with heparin because warfarin can cause birth defects.

Front 27

Two 56 year old men were admitted with severe anemia and bleeding into skin and from muscous membranes. Neither patient had ,ymphadenopathy or hepatosplenomegaly.

Patient A labs:
Hgb: 4
MCV: 110
Retics: 0.1%
Total bili: 1.6 mg/dl
Direct bili: 0.1 mg/dl
WBC: 2,000 dl with 50 segs, 0 bands, 35 lymps, 15 monos
Platelets: 15,000/dl

What is the most likely kinetic reason for the low platelet ct in pt A?
A. Decreased total platelet production
B. Ineffective production
C. Increased production
D. Redistribution

Back 27

B. Ineffective production

Front 28

Patient B labs:
Hgb: 4
MCV: 95
Retics: 0.1%
Total bili: 0.3 mg/dl
Direct bili: 0.1 mg/dl
WBC: 2,000/dl with 10 neutrophils, 85 lymphs, 5 monos
Platelets: 13,000/dl

What is the most likely kinetic reason for the low platelet ct in pt A?
A. Decreased total platelet production
B. Ineffective production
C. Increased production
D. Redistribution

Back 28

A. Decreased total platelet production

Front 29

A 20 year old woman was admitted with a 3 month history of heavy and prolonged menstrual bleeding. In addition, she had noted easy bruisability and small red spots on her legs.

PE: small scattered bruises, petechiae, purpuric lesions below the knees bilaterally. Remainder normal.
Labs:
Hgb: 12
Retics corrected: 1%
WBC: 8,500
Platelets: 5,000/dl
Total bili: 0.3 mg/dl
Direct bili: 0.1 mg/dl
The most likely reason for this patient's low platelet count is:
A. Increased destruction and decreased production
B. Increased destruction
C. Increased destruction and redistribution to enlarged spleen
D. Decreased production

Back 29

A. Decreased production and increased destruction

Front 30

All of the following lab tests would help you confirm your answer to 12.1 except?
A. Review of the peripheral blood smear
B. Mean platelet volume
C. Bone marrow examination
D. Partial thromboplastin time test

Back 30

D. Partial thromboplastin time test because it is already done with platelet-poor plasma

Front 31

Describe the difference between hypersensitivity and allergy.

Back 31

Hypersensitivity is heightened host responsiveness to normally innocuous substances. Allergy is immune-mediated hypersensitivity. Non-allergic hypersensitivity includes things like lactose intolerance and a propensity to bleed with normal aspirin use.

Front 32

Which T helper cells are important in allergy? What cytokine is involved?

Back 32

Th2 cells are important to allergy, with the involvement of IL-4.

Front 33

Describe the hypersensitivity types.

For which types are T-cells required?

Back 33

I: Allergy
II: Direct antibody-mediated (IgM and IgG)
III: Immune complex (antibody-Ag complex sticks in capillary and results in inflammation)
IV: T-cell mediated

T-cells are required for all types.

Front 34

Describe how type I hypersensitivity works.

Back 34

Allergen is picked up by an APC which presents it to a T-cell which activates a B-cell. B-cells produce IgE, which may stick to a mast cell or basophil via its Fc region. On subsequent exposure, the Ab will recognize antigen and the antibodies will be bridged and induce an inflammatory response.

Front 35

What is the feature of IgE that makes it more important in allergy than other Igs?

Back 35

Its Fc region is most important because it has a receptor on basophils and mast cells.

Front 36

What two factors are involved in regulation of IgE production? Give examples of each.

Back 36

Genetics: HLA, basal levels of IgE and FcERI

Environment: Early bacterial infection, allergen exposure, higher Th2 in newborn infants

Front 37

Describe the pathway by which immune responses begin in allergy.

Back 37

Skin is damaged -> thymic stromal lymphopoietin produced -> TSLP activates immature dendritic cells to activate Th2 cells -> Th2 cells produce IL-4, 5, 13

Front 38

What do the three cytokines produced by Th2 cells do in allergy and asthma?

Back 38

IL-4 drives B-cells to switch to IgE production.

IL-5 drives eosinophil activation.

IL-13 induces smooth muscle proliferation, mucus hypersecretion, goblet cell metaplasia, eosinophil recruitment, and fibrosis, all independent of IgE.

Front 39

Can both mast cells and basophils mediate an IgE allergic reaction?

Describe their similarities and differences.

Back 39

Yes, mast cells and basophils can both mediate IgE allergic reactions.

Both have metachromic granules, are inflammatory mediators, and express FcERI. Mast cells are mononuclear and found in the tissue, while basophils are polymorphonuclear and found in the circulation.

Front 40

What three types of inflammatory mediators are released when mast cells are activated? Include the timing of release.

Back 40

Immediate: Histamine
Short term (a few hours): Lipid metabolites, ie. prostaglandins, leukotrienes
Longer term: Cytokines

Front 41

To what cytokine are eosinophils responsive?

Back 41

IL-5

Front 42

What three diagnostic tests are available for IgE mediated allergy?

Back 42

1. Total serum IgE level
2. In vitro Ag-specific IgE (RAST)
3. In vivo Ag-specific IgE (skin test)

Front 43

Which antibody type is involved in type II hypersensitivity? What other immune molecules are involved?

Back 43

IgG and IgM

Complement is also involved.

Front 44

Name four type II hypersensitivity disorders.

Back 44

1. Autoimmune cytopenia (antibodies to RBCs, WBCs, platelets)
2. Hypo/hyperthyroidism
3. Myasthenia gravis (anti-AchR)
4. Good pasture's syndrome (anti-basement membrane in glomeruli or alveoli)

Front 45

Besides in the blood, where might type III hypersensitivity immune complexes accumulate and cause problems?

Back 45

In the joints

Front 46

Name three type III hypersensitivity disorders.

Back 46

1. Local immune complex disease: arthrus reaction to tetanus booster
2. Systemic immune complex disease: serum sickness following use of heterologous serum
3. Post-streptococcal glomerulonephritis

Front 47

Give five examples of type IV hypersensitivity disorders.

Back 47

1. Tuberculin response
2. Poison oak
3. Heavy metal contact sensitivity
4. Granulomatous reactions (TB)
5. Direct tissue injury (type II diabetes)

Front 48

How are IgE mediated diseases treated?

Back 48

Allergen avoidance, symptomatic therapy, immunomodulation, specific immunotherapy (allergy shots)

Front 49

What three classes of drugs can be used to manage allergy symptoms?

Back 49

1. Antihistamines
2. Leukotriene inhibitors
3. Bronchodilators

Front 50

What three options are available for immunomodulation to treat allergy?

Back 50

1. Corticosteroids (systemic or topical)
2. Specific immunotherapy (SIT)
3. Anti-IgE monoclonal

Front 51

What are the advantages of aerosol therapy over oral therapy?

Back 51

1. Lower dose required
2. Rapid onset of action
3. Less side effect
4. Direct delivery to airways