Bleeding Disorders- Lecture

Question 1

(Platelet bleeding/ factor bleeding) is spontaneous, immediate, superficial bleeding

Answer 1

Platelet bleeding is spontaneous, immediate, superficial bleeding
* Problem is with primary hemostasis

Question 2

Skin bleeding like petechiae is usually a symptom of (platelet/ factor) bleeding

Answer 2

Skin bleeding like petechiae is usually a symptom of platelet bleeding
* Superficial

Question 3

Mucous membrane bleeding like nosebleeds, heavy menstrual cycles, gingival bleeding are usually symptoms of (platelet/ factor) bleeding

Answer 3

Mucous membrane bleeding like nosebleeds, heavy menstrual cycles, gingival bleeding are usually symptoms of platelet bleeding

Question 4

(Platelet bleeding/ Factor bleeding) is delayed bleeding after soft platelet plug washes away

Answer 4

Factor bleeding is delayed bleeding after soft platelet plug washes away

Question 5

Hematoma (deep soft tissue bleeding) and hemarthrosis (joint bleeding) are signs of (platelet/ factor) bleeding

Answer 5

Hematoma (deep soft tissue bleeding) and hemarthrosis (joint bleeding) are signs of factor bleeding

Question 6

Thrombocytopenia < 50,000 platelets is associated with _ symptoms

Answer 6

Thrombocytopenia < 50,000 platelets is associated with easy bruising, petechiae

Question 7

Thrombocytopenia < 10,000 platelets is associted with _

Answer 7

Thrombocytopenia < 10,000 platelets is associted with spontaneous bleeding

Question 8

Normal platelet count is _

Answer 8

Normal platelet count is 150-450 cells

Question 9

The most common inherited bleeding disorder is _

Answer 9

The most common inherited bleeding disorder is von willibrand disease

Question 10

von Willibrand disease is most commonly inherited in a _ pattern

Answer 10

von Willibrand disease is most commonly autosomal dominant

Question 11

Name the primary triad of sx associated with von willibrand disease

Answer 11

vWBD is usually mild with mucocutaneous bleeding

1. heavy menstrual bleeding
2. epistaxis
3. easy bruising

Question 12

vWF is primarily produced in _ cells

Answer 12

vWF is primarily produced in endothelial cells within weibel-palade bodies
* Can also be made by platelets in alpha granules

Question 13

Two functions of vWF

Answer 13

1. vWF binds platelets to the SEC via GP1b
2. vWF stabilizes VIII in the circulation and prevents its degradation

Question 14

von Willebrand disease can be called a “mixed platelet and coagulation disorder” explain

Answer 14

Defect in vWF –> inability to form platelet plug
AND: reduced factor VIII levels

Question 15

_ is the most common type of von Willebrand disease

Answer 15

Type I is the most common type of von Willebrand disease –> quantitative defect

Question 16

Type I vWBD is caused by a _

Answer 16

Type I WBD is caused by a decreased production of vWF

Question 17

Type 2A, 2B, 2M vWBD are considered _ disorders

Answer 17

Type 2A, 2B, 2M vWBD are considered qualitative disorders

Question 18

Type 3 vWBD is associated with a _

Answer 18

Type 3 vWBD is associated with a complete lack of vWF
* Very rare- autosomal recessive

Question 19

Type 2B vWBD is _

Answer 19

Type 2B vWBD is hyperfunctional high molecular weight multimers –> spontaneous platelet aggregation –> unintented decrease in vWF
* We end up using up all of our vWF

Question 20

What lab values would we expect to see in vWBD?

Answer 20

Question 21

_ is a medication that can be given to patients with von willebrand disease to increase the release of vWF from weibel palade bodies within the endothelial cells

Answer 21

Desmopressen is a medication that can be given to patients with von willebrand disease to increase the release of vWF from weibel palade bodies within the endothelial cells

Question 22

If a patient with von Willebrand disease is being treated with desmopressin and is not improving it probably indicates _

Answer 22

If a patient with von Willebrand disease is being treated with desmopressin and is not improving it probably indicates patient has a qualitative defect in vWF
* Desmopressin is only useful in type I vWBD
* Only useful if patients have residual endothelial storage of vWF

Question 23

The most common factor deficiency is _ which is _

Answer 23

The most common factor deficiency is factor 8 which is hemophilia A

Question 24

Hemophilia B is a mutation in the factor _ gene

Answer 24

Hemophilia B is a mutation in the factor IX gene

Question 25

Hemophilia C is a mutation in the factor _ gene

Answer 25

Hemophilia C is a mutation in the **factor XI gene**

Question 26

Inheritance of hemophilia A and B

Answer 26

Inheritance of hemophilia A and B: **x-linked recessive** * Heterozygous females are carriers but really they have *mild hemophilia* * Most commonly seen in males

Question 27

Females with more extreme low levels of VIII may have _

Answer 27

Females with more extreme low levels of VIII may have **lyonization** (inactivation of one of the X chromosomes)

Question 28

Hemophilia C has _ inheritence

Answer 28

Hemophilia C has **autosomal recessive** inheritence

Question 29

The _ can be prolonged in hemophilia A or B but will correct with a _

Answer 29

The **PTT** can be prolonged in hemophilia A or B but will correct with a **mixing study**

Question 30

Two options to treat hemophilias:

Answer 30

1. Factor 8, 9, 11 concentrates 2. Desmopressin (hemophilia A)- vWF increases the stability of vWF

Question 31

_ is an inherited defect in the GP1b receptor

Answer 31

**Bernard-Soulier syndrome** is an inherited defect in the GP1b receptor * Prevents platelet binding to vWF

Question 32

_ is an inherited defect in the GPIIb/ IIIa receptor

Answer 32

**Glanzmann thrombasthenia** is an inherited defect in the GPIIb/ IIIa receptor * Prevents fibrinogen from binding platelets together

Question 33

(Bernard-Soulier/ Glanzmann) will present with large platelets on blood smear

Answer 33

**Bernard-Soulier** will present with large platelets on blood smear

Question 34

_ is an inherited disorder that leads to reduced or absent alpha granules

Answer 34

**Gray platelet syndrome** is an inherited disorder that leads to reduced or absent alpha granules * Cannot make platelet plugs * Large, gray platelets on PB smear

Question 35

_ and _ are two inherited delta-granule disorders

Answer 35

**Hermansky Pudlak syndrome** and **Chediak Higashi syndrome** are two inherited delta-granule disorders * Both are autosomal recessive

Question 36

Patient presents with hypopigmentation and dysfunction of their platelets (on PB smear), pulmonary fibrosis, colitis, neutropenia, and immunodeficiency

Answer 36

Patient presents with hypopigmentation and dysfunction of their platelets (on PB smear), pulmonary fibrosis, colitis, neutropenia, and immunodeficiency: **Hermansky Pudlak syndrome** * Autosomal recessive delta granule deficiency

Question 37

Patient presents with recurrent bacterial infections, neuropathy, ataxia, and oculocutaneous albinism and platelet dysfunction

Answer 37

Patient presents with recurrent bacterial infections, neuropathy, ataxia, and oculocutaneous albinism and platelet dysfunction: **Chediak higashi syndrome**

Question 38

Uremia (typically from renal failure) has the effect of interrupting _ and can therefore increase bleeding risk

Answer 38

Uremia (typically from renal failure) has the effect of interrupting **GPIIb/ GPIIIa (receptor aggregation)** and can therefore increase bleeding risk

Question 39

_ is a medication that decreases thromboxane A2 and decreases platelet aggregation; _ is a medication that prevents fibrinogen from binding GPIIb/IIIa receptors

Answer 39

**Aspirin** is a medication that decreases thromboxane A2 and decreases platelet aggregation; **Clopidogrel** is a medication that prevents fibrinogen from binding GPIIb/IIIa receptors

Question 40

Bernard-Soulier

Answer 40

Question 41

Glanzmann thrombasthenia

Answer 41

Question 42

Gray platelet syndrome

Answer 42

Question 43

delta-granule deficiency

Answer 43

Question 44

vWBD

Answer 44

Question 45

Triad of HELLP syndrome

Answer 45

HELLP: 1. Hemolysis 2. Elevated Liver enzymes 3. Low Platelets *associated with pre-eclampsia in pregnant women*

Question 46

HELLP syndrome, hypertensive emergencies, and prosthetic heart valves can all lead to _

Answer 46

HELLP syndrome, hypertensive emergencies, and prosthetic heart valves can all lead to **microangiopathic hemolytic anemia** --> schistocytes on PB smear

Question 47

Explain the mechanism of DIC

Answer 47

1. Something triggers the **coagulation cascade** to be *hyperactive* 2. **Unnecessary fibrin** forms in vessels all over the body 3. Fibrin gets **lodged in small vessels** 4. Platelets join fibrin and form **small thrombi** 5. We begin to **exhaust our platelets and clotting factors** --> bleeding 6. **RBCs are getting ripped apart** as they go past thrombi --> schistocytes

Question 48

We can identify DIC on peripheral blood smear by the presence of _

Answer 48

We can identify DIC on peripheral blood smear by the presence of **helmet cells, schistocytes**

Question 49

Clinical manifestations of DIC

Answer 49

* Oozing from puncture sites * Petechiae * Thrombocytopenia * Respiratory failure * Seizures, coma * Acute renal failure, cardiovascular collapse

Question 50

Classic causes of DIC

Answer 50

Classical causes of DIC: * Snake venom * Gram-negative bacteria sepsis * Trauma/ burns * Acute promyelocytic leukemia * Vasculitis **"MOST" : malignancy, obstetrics, spesis, trauma**

Question 51

4 key laboratory findings associated with DIC

Answer 51

1. **Schistocytes** 2. **Prolonged PT, PTT, INR, TT** (due to the consumption of coagulation factors) 3. **Elevated D-dimers** (breakdown of microthrombi) 4. **Decreased fibrinogen**

Question 52

Thrombotic thrombocytopenia purpura is caused by a deficiency in _

Answer 52

Thrombotic thrombocytopenia purpura is caused by a deficiency in **ADAMTS13** * Without ADAMTS13 we can't cleave ultra-large vWF multimers * We get excessive formation of microthrombi in small vessels --> deplete our platelets and we rip apart RBCs

Question 53

(Acquired/ Inherited) TTP is more common

Answer 53

**Acquired** TTP is more common * Results from a formation of an autoantibody that prevents ADAMTS13 from functioning normally

Question 54

Symptoms of TTP

Answer 54

Symptoms of TTP: * **MAHA**- anemia with schistocytes * **Thrombocytopenia**- petechiae and purpura * **Acute renal failure**- increased creatinine * **Fever** * **Neurologic abnormalities**- altered mental status

Question 55

One treatment option of TTP includes removing defective ADAMTS13 and replacing with normal ADAMTS13 via _

Answer 55

One treatment option of TTP includes removing defective ADAMTS13 and replacing with normal ADAMTS13 via **therapeutic plasma exchange**

Question 56

We can also treat TTP with a monoclonal ab fragment medication called _ that binds to vWF and blocks its interaction with platelets to prevent microthrombi formation

Answer 56

We can also treat TTP with a monoclonal ab fragment medication called **caplacizumab** that binds to vWF and blocks its interaction with platelets to prevent microthrombi formation

Question 57

We can also treat acquired TTP with a medication to suppress the immune system such as _ or _

Answer 57

We can also treat acquired TTP with a medication to suppress the immune system such as **glucocorticoids** or **rituximab**

Question 58

_ is a condition in which bacterial toxins cause damage to the endothelium and lead to platelet activation and aggregation

Answer 58

**Hemolytic uremic syndrome** is a condition in which bacterial toxins cause damage to the endothelium and lead to platelet activation and aggregation * E.Coli O157:H7 * Shiga toxin

Question 59

Triad of Sx associated with HUS

Answer 59

1. Hemolytic microangiopathic anemia 2. Thrombocytopenia 3. Acute renal failure *Shares all of these symptoms with TTP*

Question 60

What is unique about HUS that distinguishes it from TTP?

Answer 60

HUS is usually associated with **bloody diarrhea** * Question stems often include "child ate a burger"

Question 61

DIC: Platelet count PT PTT Fibrinogen

Answer 61

DIC: Platelet count **decreased** PT **increased** PTT **increased** Fibrinogen **decreased** *Note: DIC thrombi are composed of platelets and fibrin so we see consumption of coagulation factors*

Question 62

TTP or HUS Platelet count PT PTT Fibrinogen

Answer 62

TTP or HUS Platelet count **decreased** PT **normal** PTT **normal** Fibrinogen **normal** *Note that the thrombi are mostly composed of platelets --> no consumption of coagulation factors*

Question 63

Immune thrombocytopenia (ITP) is caused by _

Answer 63

Immune thrombocytopenia (ITP) is caused by **autoantibodies to platelet glycoproteins (GPIIb/ GPIIIa)** * Platelets get sent to the splenic macrophages for destruction --> thrombocytopenia * Mild cases: easy bruising * Severe cases: large areas of bleeding in the skin

Question 64

Chronic ITP is most common in _ populations

Answer 64

Chronic ITP is most common in **adult women < 40** * It is often secondary to lupus, HIV, infection * Sx: petechiae, heavy menstrual bleeding, easy bruising

Question 65

Acute ITP is most common in _ populations

Answer 65

Acute ITP is most common in **children following a viral illness** * The antibodies generated against infection are cross-reacting with platelets * Usually self limiting * Sx: petechiae, bruising, bleeding, abrupt onset

Question 66

How would ITP present on peripheral blood smear and bone marrow biopsy

Answer 66

* Larger platelets on smear * Increased immature (small) megakaryocytes on bone marrow biopsy

Question 67

What does this indicate?

Answer 67

Error in blood collection

Question 68

Treatment options for ITP

Answer 68

* Steroids * IVIG * Platelet transfusions * Thrombopoietin receptor agonist * Splenectomy