Pathoma - Secondary Hemostasis & Related Disorders - Fundamentals Of Pathology

Front 1

What is the goal of secondary hemostasis? How does it occur?

Back 1

Stabilize the weak platelet plug. This occurs via the coagulation cascade.

Front 2

The coagulation cascade generates thrombin. What happens next?

Back 2

Thrombin converts fibrinogen in the PLT plug to fibrin. Fibrin is then cross-linked, yielding a stable platelet-fibrin thrombus.

Front 3

Activation of coagulation factors requires [...]

Back 3

(1) Exposure to an activating substance
(2) Phospholipid surface
(3) Calcium

Front 4

In what granules are calcium contained in PLTs?

Back 4

Dense core granules

Front 5

Disorders due to secondary hemostasis is usually due to ______________.

Back 5

factor abnormalities.

Front 6

Clinical features of secondary hemostasis disorders include [...]

Back 6

(1) Deep tissue bleeding into muscles and joints
(2) Rebleeding after surgical procedure (such as wisdom tooth extraction)

Front 7

PT measures _________ and ____________.

Back 7

extrinsic; common pathways

Front 8

PTT measures __________ and ___________.

Back 8

intrinsic; common

Front 9

Draw a simple coagulation cascade.

Back 9

Front 10

What is an easy way of remembering that PTT is useful for monitoring heparin therapy?

Back 10

PTT = HEP (three letters)

Front 11

Hemophilia A is a genetic deficiency in factor ____.

Back 11

FVIII (Hemophilia AAAIGHT/EEEEEIGHT)

Front 12

What is the hereditary pattern of hemophilia A?

Back 12

X-linked recessive; predominantly affects males

Front 13

Hemophilia A can arise from a __________ without any family history.

Back 13

new mutation... it can arise de novo in an offspring without any family history

Front 14

Classical clinical features of a male with hemophilia A would include?

Back 14

(1) Deep tissue bleeding
(2) Joint bleeding
(3) Postsurgical bleeding

Depends on degree of severity.

Front 15

What are laboratory findings in hemophilia A?

Back 15

(1) Increased PTT, normal PT
(2) Decreased FVIII
(3) Normal platelet count and bleeding time

Front 16

What is the treatment of Hemophilia A?

Back 16

Recombinant FVIII

Front 17

Hemophilia B is due to?

Back 17

Genetic FIX deficiency. ("One more" than hemophilia A)

Front 18

How does hemophilia B present clinically compared to hemophilia A?

Back 18

Resembles hemophilia A, except FIX levels are decreased instead of FVIII.

Front 19

What is a coagulation factor inhibitor?

Back 19

Autoantibody against coagulation factors

Front 20

The MC coagulation factor inhibitor is [...]

Back 20

Anti-FVIII

Front 21

How would you distinguish between coagulation factor inhibitor anti-FVIII in a patient with hemophilia A?

Back 21

Mixing study. Mix plasma with normal plasma. If it correct, it is hemophilia (you replenish VIII), if it doesn't, it is due to coagulation factor inhibitor because the replenished VIII will just be bound.

Front 22

This is the MC inherited coagulation disorder.

Back 22

Von Willebrand Disease

Front 23

True or false: Von Willebrand Disease is only one disease entity.

Back 23

False. Multiple subtypes exist. Cause can be quantitative or qualitative.

Front 24

The MC type of vWF disease is ______________________.

Back 24

AD with decreased vWF levels

Front 25

Patients with vWF disease will present with ________ and ___________ because low vWF impairs ____________.

Back 25

mild mucosal bleeding; skin bleeding; platelet adhesion

Front 26

What would the laboratory findings in vWF disease be?

Back 26

(1) Increased bleeding time
(2) Increased PTT, normal PT
(3) Abnormal ristocetin test

Front 27

What happens when you add ristocetin to a medium containing normal healthy platelets?

Back 27

They aggregate in the presence of vWF. In its absence, they don't.

Front 28

The treatment of vWF is ___________.

Back 28

Desmopressin. It increases vWF release from Weibel-Palade bodies of endothelial cells.

Front 29

Deficiency of vitamin K occurs in [...]

Back 29

(1) Newborns.
- Lack bacterial colonization of the bowel.

(2) Long-term antibiotic therapy.
- Killing off the gut flora

(3) Malabsorption
- Fat soluble vitamin

Front 30

Breast milk contains __________ (adequate/very little) vitamin K.

Back 30

very little

Front 31

Failure of what organ can cause a secondary hemostatic disease, and by what pathomechanisms?

Back 31

Liver.

(1) Decreased production of coagulation factors
(2) Decreased activation of vitamin K by epoxide reductase.

Front 32

Measuring the effect of liver failure on coagulation is done using __________.

Back 32

PT

Front 33

What is large-volume transfusion?

Back 33

You dilute coagulation factors, resulting in a relative deficiency.

Front 34

Vitamin K levels normally decrease between days ___ and ____.

Back 34

2;5

Front 35

What is given to newborns after they are born?

Back 35

Prophylactic shot of vitamin K.

Front 36

What is a disease that may lead to malabsorption of vitamin K?

Back 36

Celiac disease

Front 37

Rat poison contains _________.

Back 37

warfarin

Front 38

A young child has been staying with his grandparents for a week. The grandparents brings the child your office after several bouts of epistaxis and easy bruising. The child is now hypotensive. What could you suspect?

Back 38

Exposure to warfarin from elders

Front 39

This is the MCC of thrombocytopenia in hospitalized patients.

Back 39

Heparin-induced thrombocytopenia.

Front 40

How can heparin cause thrombocytopenia?

Back 40

Heparin can bind to platelet factor 4 on platelets, forming a complex. Autoantibodies can be formed against this complex, leading to destruction.

Front 41

What is a feared complication of heparin-induced thrombocytopenia?

Back 41

When it occurs, fragments of destroyed PLTs may activate remaining PLTs leading to thrombosis.

Front 42

What anticoagulant do you NOT wanna give HIT-patients complicated with thrombosis?

Back 42

Warfarin. In these patients there is an increased risk of coumadin skin necrosis.

Front 43

What is the problem in DIC and what is the result?

Back 43

Pathologic activation of the coagulation cascade. Widespread microthrombi result in ischemia and infarction. Consumption of PLTs and factors, bleeding results, especially from IV sites and mucosal surface (e.g. coughing up blood, hematuria, hematochezia).

Front 44

DIC is almost always __________ (primary/secondary).

Back 44

DIC is almost always secondary to another disease process.

Front 45

List five disease processes that may lead to DIC.

Back 45

(1) Obstetric complication
(2) Sepsis
(3) AdenoCA
(4) Acute promyelocytic leukemia
(5) Rattlesnake bite

Front 46

Why can obstetric complications lead to DIC?

Back 46

Amniotic fluid contains tissue factor which activates the coagulation cascade.

Front 47

How can sepsis lead to DIC?

Back 47

(1) Endotoxin can activate coagulation cascade
(2) Macrophages produce inflammatory mediators activating coagulation indirectly

Front 48

How can adenocarcinoma cause DIC?

Back 48

Mucin from adenocarcinoma can activate the coagulation cascade, especially if it is metastatic.

Front 49

How can acute promyelocytic leukemia cause DIC?

Back 49

Cells are loaded with primary granules. They coalesce to form Auer rods. When they enter the circulation they can activate coagulation.

Front 50

A rattlesnake bite can cause DIC by ______________.

Back 50

injecting venom (cytohemoneurotoxin) that causes DIC. Seen with rattlesnakes, copperheads (nordamerikansk giftslange) and water moccasin (seen in southeastern US).

Front 51

What are some laboratory findings in DIC?

Back 51

(1) Low PLT
- We are consuming PLTs.
(2) Increased PT/PTT
- Everything is consumed
(3) Decreased fibrinogen
- It's used up
(4) Microangiopathic hemolytic anemia
- Microthrombi will "sheer" RBCs
(5) Elevated fibrin split products (D-dimer)

Front 52

Treatment of DIC involves [...]

Back 52

(1) Addressing the underlying cause
(2) Transfuse blood products
(3) Cryoprecipitate

Front 53

What is fibrinolysis?

Back 53

End-stage of coagulation. It's removal of a thrombus by lysing it.

Front 54

Disorders of fibrinolysis occurs due to _____________.

Back 54

plasmin overactivity resulting in excessive cleavage of fibrinogen

Front 55

What is the action of plasmin after being activated by tissue plasminogen activator?

Back 55

(1) Cleaves fibrin
(2) Cleaves serum fibrinogen
(3) Destroys coagulation factors
(4) Blocks PLT aggregation

Front 56

What molecule inactivates plasmin?

Back 56

alpha2-antiplasmin

Front 57

Provide two scenarios that may cause disorder of fibrinolysis.

Back 57

Radical prostatectomy - In this setting, urokinase is released from the tissue causing activation of plasminogen and the release of plasmin.

Cirrhosis of liver - reduced production of alpha2-antiplasmin

Front 58

Patients with disorders of fibrinolysis present the same way as a patient with ___________.

Back 58

DIC. They present with increased bleeding.

Front 59

What are the laboratory findings in disorders of fibrinolysis?

Back 59

Increased PT/PTT
- Action of plasmin on coagulation factors.

Increased bleeding time (but normal PLT count)
- Plasmin inhibits platelet aggregation

Increased fibrinogen split products without D-dimer.

Front 60

Which one of these situations causes increase in D-dimer:

A. Plasmin cleaves a thrombus
B. Plasmin cleaves fibrinogen

Back 60

A.

Front 61

The treatment of disorders of fibrinolysis is? How does it work?

Back 61

Aminocaproic acid. It blocks the activation of plasminogen.