Bleeding Disorders- Lecture Flashcards
(Platelet bleeding/ factor bleeding) is spontaneous, immediate, superficial bleeding
Platelet bleeding is spontaneous, immediate, superficial bleeding
* Problem is with primary hemostasis
Skin bleeding like petechiae is usually a symptom of (platelet/ factor) bleeding
Skin bleeding like petechiae is usually a symptom of platelet bleeding
* Superficial
Mucous membrane bleeding like nosebleeds, heavy menstrual cycles, gingival bleeding are usually symptoms of (platelet/ factor) bleeding
Mucous membrane bleeding like nosebleeds, heavy menstrual cycles, gingival bleeding are usually symptoms of platelet bleeding
(Platelet bleeding/ Factor bleeding) is delayed bleeding after soft platelet plug washes away
Factor bleeding is delayed bleeding after soft platelet plug washes away
Hematoma (deep soft tissue bleeding) and hemarthrosis (joint bleeding) are signs of (platelet/ factor) bleeding
Hematoma (deep soft tissue bleeding) and hemarthrosis (joint bleeding) are signs of factor bleeding
Thrombocytopenia < 50,000 platelets is associated with _ symptoms
Thrombocytopenia < 50,000 platelets is associated with easy bruising, petechiae
Thrombocytopenia < 10,000 platelets is associted with _
Thrombocytopenia < 10,000 platelets is associted with spontaneous bleeding
Normal platelet count is _
Normal platelet count is 150-450 cells
The most common inherited bleeding disorder is _
The most common inherited bleeding disorder is von willibrand disease
von Willibrand disease is most commonly inherited in a _ pattern
von Willibrand disease is most commonly autosomal dominant
Name the primary triad of sx associated with von willibrand disease
vWBD is usually mild with mucocutaneous bleeding
- heavy menstrual bleeding
- epistaxis
- easy bruising
vWF is primarily produced in _ cells
vWF is primarily produced in endothelial cells within weibel-palade bodies
* Can also be made by platelets in alpha granules
Two functions of vWF
- vWF binds platelets to the SEC via GP1b
- vWF stabilizes VIII in the circulation and prevents its degradation
von Willebrand disease can be called a “mixed platelet and coagulation disorder” explain
Defect in vWF –> inability to form platelet plug
AND: reduced factor VIII levels
_ is the most common type of von Willebrand disease
Type I is the most common type of von Willebrand disease –> quantitative defect
Type I vWBD is caused by a _
Type I WBD is caused by a decreased production of vWF
Type 2A, 2B, 2M vWBD are considered _ disorders
Type 2A, 2B, 2M vWBD are considered qualitative disorders
Type 3 vWBD is associated with a _
Type 3 vWBD is associated with a complete lack of vWF
* Very rare- autosomal recessive
Type 2B vWBD is _
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
What lab values would we expect to see in vWBD?
_ 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
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
If a patient with von Willebrand disease is being treated with desmopressin and is not improving it probably indicates _
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
The most common factor deficiency is _ which is _
The most common factor deficiency is factor 8 which is hemophilia A
Hemophilia B is a mutation in the factor _ gene
Hemophilia B is a mutation in the factor IX gene
Hemophilia C is a mutation in the factor _ gene
Hemophilia C is a mutation in the factor XI gene
Inheritance of hemophilia A and B
Inheritance of hemophilia A and B: x-linked recessive
* Heterozygous females are carriers but really they have mild hemophilia
* Most commonly seen in males
Females with more extreme low levels of VIII may have _
Females with more extreme low levels of VIII may have lyonization
(inactivation of one of the X chromosomes)
Hemophilia C has _ inheritence
Hemophilia C has autosomal recessive inheritence
The _ can be prolonged in hemophilia A or B but will correct with a _
The PTT can be prolonged in hemophilia A or B but will correct with a mixing study
Two options to treat hemophilias:
- Factor 8, 9, 11 concentrates
- Desmopressin (hemophilia A)- vWF increases the stability of vWF
_ is an inherited defect in the GP1b receptor
Bernard-Soulier syndrome is an inherited defect in the GP1b receptor
* Prevents platelet binding to vWF
_ is an inherited defect in the GPIIb/ IIIa receptor
Glanzmann thrombasthenia is an inherited defect in the GPIIb/ IIIa receptor
* Prevents fibrinogen from binding platelets together
(Bernard-Soulier/ Glanzmann) will present with large platelets on blood smear
Bernard-Soulier will present with large platelets on blood smear
_ is an inherited disorder that leads to reduced or absent alpha granules
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
_ and _ are two inherited delta-granule disorders
Hermansky Pudlak syndrome and Chediak Higashi syndrome are two inherited delta-granule disorders
* Both are autosomal recessive
Patient presents with hypopigmentation and dysfunction of their platelets (on PB smear), pulmonary fibrosis, colitis, neutropenia, and immunodeficiency
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
Patient presents with recurrent bacterial infections, neuropathy, ataxia, and oculocutaneous albinism and platelet dysfunction
Patient presents with recurrent bacterial infections, neuropathy, ataxia, and oculocutaneous albinism and platelet dysfunction: Chediak higashi syndrome
Uremia (typically from renal failure) has the effect of interrupting _ and can therefore increase bleeding risk
Uremia (typically from renal failure) has the effect of interrupting GPIIb/ GPIIIa (receptor aggregation) and can therefore increase bleeding risk
_ is a medication that decreases thromboxane A2 and decreases platelet aggregation;
_ is a medication that prevents fibrinogen from binding GPIIb/IIIa receptors
Aspirin is a medication that decreases thromboxane A2 and decreases platelet aggregation;
Clopidogrel is a medication that prevents fibrinogen from binding GPIIb/IIIa receptors
Bernard-Soulier
Glanzmann thrombasthenia
Gray platelet syndrome
delta-granule deficiency
vWBD
Triad of HELLP syndrome
HELLP:
1. Hemolysis
2. Elevated Liver enzymes
3. Low Platelets
associated with pre-eclampsia in pregnant women
HELLP syndrome, hypertensive emergencies, and prosthetic heart valves can all lead to _
HELLP syndrome, hypertensive emergencies, and prosthetic heart valves can all lead to microangiopathic hemolytic anemia –> schistocytes on PB smear
Explain the mechanism of DIC
- Something triggers the coagulation cascade to be hyperactive
- Unnecessary fibrin forms in vessels all over the body
- Fibrin gets lodged in small vessels
- Platelets join fibrin and form small thrombi
- We begin to exhaust our platelets and clotting factors –> bleeding
- RBCs are getting ripped apart as they go past thrombi –> schistocytes
We can identify DIC on peripheral blood smear by the presence of _
We can identify DIC on peripheral blood smear by the presence of helmet cells, schistocytes
Clinical manifestations of DIC
- Oozing from puncture sites
- Petechiae
- Thrombocytopenia
- Respiratory failure
- Seizures, coma
- Acute renal failure, cardiovascular collapse
Classic causes of DIC
Classical causes of DIC:
* Snake venom
* Gram-negative bacteria sepsis
* Trauma/ burns
* Acute promyelocytic leukemia
* Vasculitis
“MOST” : malignancy, obstetrics, spesis, trauma
4 key laboratory findings associated with DIC
- Schistocytes
- Prolonged PT, PTT, INR, TT (due to the consumption of coagulation factors)
- Elevated D-dimers (breakdown of microthrombi)
- Decreased fibrinogen
Thrombotic thrombocytopenia purpura is caused by a deficiency in _
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
(Acquired/ Inherited) TTP is more common
Acquired TTP is more common
* Results from a formation of an autoantibody that prevents ADAMTS13 from functioning normally
Symptoms of TTP
Symptoms of TTP:
* MAHA- anemia with schistocytes
* Thrombocytopenia- petechiae and purpura
* Acute renal failure- increased creatinine
* Fever
* Neurologic abnormalities- altered mental status
One treatment option of TTP includes removing defective ADAMTS13 and replacing with normal ADAMTS13 via _
One treatment option of TTP includes removing defective ADAMTS13 and replacing with normal ADAMTS13 via therapeutic plasma exchange
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
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
We can also treat acquired TTP with a medication to suppress the immune system such as _ or _
We can also treat acquired TTP with a medication to suppress the immune system such as glucocorticoids or rituximab
_ is a condition in which bacterial toxins cause damage to the endothelium and lead to platelet activation and aggregation
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
Triad of Sx associated with HUS
- Hemolytic microangiopathic anemia
- Thrombocytopenia
- Acute renal failure
Shares all of these symptoms with TTP
What is unique about HUS that distinguishes it from TTP?
HUS is usually associated with bloody diarrhea
* Question stems often include “child ate a burger”
DIC:
Platelet count
PT
PTT
Fibrinogen
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
TTP or HUS
Platelet count
PT
PTT
Fibrinogen
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
Immune thrombocytopenia (ITP) is caused by _
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
Chronic ITP is most common in _ populations
Chronic ITP is most common in adult women < 40
* It is often secondary to lupus, HIV, infection
* Sx: petechiae, heavy menstrual bleeding, easy bruising
Acute ITP is most common in _ populations
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
How would ITP present on peripheral blood smear and bone marrow biopsy
- Larger platelets on smear
- Increased immature (small) megakaryocytes on bone marrow biopsy
What does this indicate?
Error in blood collection
Treatment options for ITP
- Steroids
- IVIG
- Platelet transfusions
- Thrombopoietin receptor agonist
- Splenectomy
