7. Hematologic Disorders Flashcards
Hemostasis
Primary hemostasis
Platelet ____
Secondary hemostasis
____ cascade
____ formation
aggregation/plug
coagulation
fibrin
Platelets
____ cell fragments from ____
150-400 million/mL of blood
Average life around ____ days
anuclear
megakaryocytes
7-10
Platelet aggregation and formation of platelet plug
____
____
____
adhesion
activation
aggregation
Primary Hemostasis
Endothelial damage
____ exposure- vWF, TF, laminin, fibronectin
Platelet Adhesion
____ binds Von Willebrand Factor
____ produced by endothelial cells, catches platelets
GP1b deficiency- ____
collagen
GP Ib-IX-V
vWF
bernard-soulier
Platelet activation
Caused by adhesion to ECM
Leads to degranulation and conformational change
Degranulation
____ granules- vWF, fibrinogen, FV, FXIII
____ granules- ADP, serotonin
Phospholipid membrane metabolism
Arachidonic acid release eventually leads to ____-> platelet activation and ____
____ and ____- platelet recruitment and activation
alpha
dense
thromboxane A2
aggregation
ADP
thromboxane A2
Formation of Thromboxane
This is basically the breakdown of phospholipids.
• •
•
You have ____ which makes arachidonic acid.
Then you have these cox 1 and cox 2 that break down arachidonic acid into ____ and all these diff prostaglandins can cause through thromboxane synthase release of thromboxane A2 which activates the ____.
Also ____ which is important in inflammation.
____ which is kind of a protective prostaglandin within your gut if you remember that.
So this is the breakdown of phospholipid membranes and its important because some meds impact this and impact platelet activation and aggregation which is the whole point of why you’re taking these medications
phospholipase A2
prostaglandins
platelets
prostacyclines
PGE2
Platelet Activation
So again this is kind of a picture format of this.
• The platelet adheres to the ____. It becomes activated, the release of these
granules, the alpha and dense granules, that release ____ and serotonin which act on itself creating a ____ feedback mechanism that further activates platelets in the area and causes platelet aggregation.
• If you’ll note, the ADP interacts with the ____ receptor which we’ll talk about down the road as well.
endothelium
ADP
positive
P2Y12
Primary Hemostasis
Platelet Aggregation
____ integrin on platelets is the receptor for fibrinogen
Platelet Plug
TF activation
GPIIb/IIIa deficiency- ____
GPIIb/IIIa
glanzman thrombasthenia
We have endothelial cell damage, these platelets are flying by, the ____ factor basically catches these platelets causing conformational change and causing platelet activations, a release of ____ and ____ through these different granules that then feed back and cause further activation and aggregation of platelets becoming a ____. Hopefully that’s a simplified way of the whole platelet plug process.
vWF
ADP
TXA2
platelet plug
Secondary hemostasis
- Fibrin clot
Secondary hemostasis once you have this ____.
This should look somewhat familiar to you, you know your intrinsic and extrinsic pathway of the coagulation cascade, all these different factors.
Basically 1 through 13. All cause in the end, the formation of ____ which then causes fibrinogen to turn into ____. fibrin is basically these strands that hold the platelet plug together and mature and help you stop bleeding.
we’ll talk about different medications and deficiencies of some of these factors that can cause bleeding.
if you know basic physiology, you can figure most of this stuff out like how medications work, why people take medications, when to stop the medications and what happens when you stop.
platelet plug
thrombin
fibrin
Fibrin clot
Fibrinogen cleaved to ____
Fibrin is ____ and crosslinks platelets
Forms a hemostatic ____ and blood clot
fibrin
insoluble
platelet plug
Lab tests
PT/INR
Tests ____ pathway
Factor ____
PTT
Tests ____ pathway
Factor ____
Bleeding time
Measures ____ function
extrinsic
I, II, V, VII, X
intrinsic
I, II, V, VIII, IX, X, XI, XII
platelet
Von Willebrand’s Disease
The most ____ hereditary coagulation abnormality
1/100 of general population
Deficiency of von Willebrand factor
vWF binds to other proteins (____/collagen)
vWF binds ____
Symptoms
____, easy bruising, nosebleeds, ____ bleeding, heavy menstrual periods
common
factor VIII
platelets
bleeding
gingival
Von Willebrand Disease
Type 1- ____ defect (85%) Failure to secrete, or cleared more quickly
Many ____ or mild symptoms
Type 2- ____ defect (15%) Type 3- ____ of production (rare)
quantitative
asymptomatic
qualitative
absence
Von Willebrand Disease
Diagnosis- Labs
____
measures amount of vWF (____)
____ activity- vWF activity Measures how well vWF works (____)
vWF multimer study
Evaluates ____
Factor VIII levels ____
____ PTT
vWF:Ag
quantitative
ristocetin cofactor
qualitative
structure
decreased
elevated
Von Willebrand Disease
Treatment-
____ (IV or IN)- minor trauma
Stimulates vWF release from ____ bodies in endothelial cells
____- major trauma
____ vWF
Cryoprecipitate
____, vWF, ____, XIII, ____
Transfusions
dDAVP
weibel palade
factor VIII
recombinant
fibrinogen
VIII
fibronectin
Hemophilia
Hemophilia A
____ deficiency (____)
~____% of hemophilia cases
30% caused by new mutations
Hemophilia B
Factor ____ deficiency (____) ~20% of hemophilia cases
Hemophilia C
Factor ____ deficiency (____)
factor VIII
x-linked recessive
80
IX
X-linked recessive
XI
autosomal
Hemophilia
Signs/Symptoms Variable Internal \_\_\_\_ Hemarthrosis, Muscle/soft tissue, Retroperitoneal Petechiae characteristically \_\_\_\_
Complications
____ damage
Transfusion reactions
____ hemorrhage
bleeding
absent
joint
intracranial
Hemophilia labs
Bleeding Time
____
Prothrombin/INR
____
PTT
____
Factor ____ and ____ assays to confirm diagnosis
normal
normal
prolonged
VIII
IX
Again hemophilia’s basically with factor ____ and factor ____ which is within your clotting cascade.
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