Qualitative Platelet Disorders Flashcards
What is this describing:
- increased bleeding time in the presence of a normal platelet count
qualitative platelet disorders
What are some clinical manifestations of qualitative platelet disorders?
- petechiae
- purpura
- mucosal bleeding
- gingival bleeding
- spontaneous bruising
- Qualitative platelet disorders may be (…) or (…)
- congenital or acquired
What are some causes of acquired qualitative platelet disorders?
- drug effects
- systemic inflammatory conditions
- hematologic conditions
What is required for hemostasis?
- healthy endothelium (doesn’t expose collagen/no inflammation)
- functioning platelets
- von willebrand factor (VWF)
- adequate clotting/anticlotting factors
What is the general presentation of qualitative platelet disorders?
- excessive or repetitive bleeding
- bleeding at unusual sites:
** petechiae, bruising, mucosal bleeding
** hemarthroses and deep tissue hematomas (more common in coag disorders)
** purpura
What are the different mechanisms of qualitative platelet dysfunction?
(prolonged bleeding can result from alterations in platelet function)
- adhesion between platelets and the vessel wall
- platelet-platelet adhesion
- platelet granule secretion
- arachidonic acid pathway activity
- membrane phospholipid regulation
What disorders cause congenital qualitative platelet disorders?
- von willebrand disease (vWD)
- Bernard-Soulier syndrome
- Glanzmann thrombosthenia
What is the most common disorder leading to congenital qualitative platelet disorders?
vWD
What can cause acquired qualitative platelet disorders?
- drug induces (ASA, NSAIDs)
- uremia
- myeloproliferative/myelodysplastic disorders
- chronic inflammatory disorders
Which is more common, congenital or acquired qualitative platelet disorders?
acquired
What is the most common cause of acquired qualitative platelet disorders?
ASA and other NSAIDs and antiplatelet agents
Congenital qualitative platelet disorders will have mostly (…) platelet counts, but (…) bleeding times
- normal
- prolonged
In qualitative platelet disorders, often times platelet numbers are (…) but function studies are (…)
- normal
- abnormal
What is the general treatment for qualitative platelet disorders?
- discontinue offending agent/drug
- dialysis for uremia, renal failure
- platelet transfusion prn
- vWD specific treatment
- Describe Von Willebrand disease?
- How does someone get VWD?
- This causes a bleeding disorder that slows the (…), causing prolonged (…)
- a deficiency in, or impairment of, von willebrand factor
- usually inherited (autosomal dominant) but can be acquired (rare)
- blood clotting process, prolonged bleeding after an injury
People with VWD often experience what signs/symptoms?
- easy bruising
- long-lasting nosebleedings
- excessive bleeding or oozing following an injury, surgery, or dental work
If a patient complains of excessive bleeding following a dental procedure, what is the most likely diagnosis?
VWD
What is a plasma glycoprotein that mediates platelet adhesion and aggregation at sites of vascular injury?
von willebrand factor
Where can you find VWF in the body?
- circulating in the blood
- stored in endothelial cells
- platelets
VWF binds to (…) resulting in the exposure of platelet binding domains to promote binding of platelets to (…)
- injured (nonendothelial) blood vessels
- vessel bound vWF
What does VWF carry and what does this do?
carries factor VIII which increases its half life
- What type of deficiency will there be in a patient with VWD?
- This is either caused by a (…) or (…)
- This leads to (…) being more rapidly cleared from circulation
- factor VIII deficiency
- primary deficiency or defect of VWF
- factor VIII
Which pathway in the coagulation cascade will there be issues in if a person has VWD?
intrinsic pathway
What is the most common inherited bleeding disorder?
von willebrand disease
(1% of population)
What are the different types of VWD and how are they inherited?
- type I and II: autosomal dominant
- type III: autosomal recessive
Describe VWF levels in type I, II, and III VWD
type I: low VWF levels (partial quantitative deficiency)
type II: normal VWF levels but VWF doesn’t work correctly (qualitative deficiency)
type III: little or no VWF (total deficiency)
- What % of people with VWD have type I?
- What % of people have type III?
- 75-80%
- less than 5%
VWD affects males, women, and all ethnicities (…)
equally
What are some mucocutaneous bleeding symptoms people with VWD will have?
- easy bruising and bleeding from nose, sinuses
- prolonged or excessive bleeding from minor cuts
- GI hemorrhage or vaginal bleeding (menorrhagia)
Those with VWD will have an increased risk for bleeding after what?
- surgery
- dental extractions
- traumatic injury
- childbirth
Pertaining to VWD:
- exacerbation of bleeding symptoms following ingestion of (…) -> increase bleeding risk
- bleeding decreases with use or (…) or (…)
- symptoms can range from relatively mild or infrequent bleeding in (…) VWD to severe, life-threatening bleeding in (…) VWD
- ASA, NSAIDs
- estrogen or pregnancy
- type I VWD, type III VWD
Women with VWD may be more affected by bleeding symptoms because of hemostatic challenged of (…) and (…)
menstruation and childbirth
What are some pediatric specific bleeding signs that can give a clue to the presence of VWD?
- umbilical stump bleeding
- post-circumcision bleeding
- cephalohematoma (collection of blood in skull)
- cheek hematoma
- conjunctival bleeding
- post-venipuncture bleeding
What is the general workup for a patient suspected to have VWD?
- thorough history and physical exam; detailed family history
- CBC
- PT and PTT
- bleeding time
What will a CBC show if a person has VWD?
- low Hgb and platelets (may have mild anemia)
- platelet count usually 70-140,000
How will PT and PTT be affected in an individual with VWD?
- PT usually normal
- PTT may be prolonged (d/t factor VIII deficiency)
How will bleeding time usually be affected in an individual with VWD?
usually prolonged
What is the test of choice for platelet dysfunction problem?
bleeding time
What is the test of choice for VWD?
plasma analysis - tests for factors
- In a plasma analysis, if the factors are < 30, what is most likely the diagnosis?
- > 50 is (…)
- VWD
- normal
What is not recommended for routine screening due to low sensitivity and specificity for VWD?
platelet function analyzer
What is the treatment for VWD?
- desmopressin - DDAVP (first line)
- von willebrand factor/factor VIII (if DDAVP if ineffective or contraindicated or factor replacement necessary
What drug has antidiuretic properties similar to vasopressin and causes the release of stored VWF in the body and its effectiveness is subject to the type of VWD?
desmopressin (DDAVP)
What VWD types can we use desmopressin for?
II and III
What can we use secondary if DDAVP is ineffective or contraindicated, or factory replacement necessary, is given IV, and is effective in the prophylaxis of bleeding in surgical procedures?
von willebrand factor/factor VIII
Which VWD type is treated with VWF/factor VIII?
type III
What are some other treatment options for VWD?
- platelet transfusion (not really effective)
- anti-fibrinolytic drugs
- pregnancy
What treatment option for VWD is only used as a back up option as it contains VWF, however large volumes are needed to achieve therapeutic effects?
platelet transfusion
What is a supplemental treatment for VWD (type III) that is taken orally, topically, or IV to treat mild mucocutaneous bleeding and is the main treatment for BSS and thrombasthenia?
anti-fibrinolytic drugs
- (…) naturally increase in pregnancy so (…) could be at normal levels
- You should closely monitor pregnant mothers with (…) and (…) for hemorrhaging
- Most will not need treatment during pregnancy, but will (…) easier after delivery
- VWF levels; VWF type I
- type II and III VWD
- bleed easier
What should patients avoid if they have VWD?
- aspirin or medications that contain aspirin
- activities with risk of hemorrhage
What are some congenital qualitative platelet disorders that include hereditary defects in platelet function which can occur at all stages of the linked sequence of events involved in hemostatic platelet activation at sites of vascular injury?
- platelet adhesion (bernard-soulier syndome)
- platelet release
- platelet aggregation (glanzmann thrombasthenia)
(these lead to varying levels of severity of bleeding)
- What syndrome describes a defect in platelet adhesion?
- How is this inherited?
- This is a defect in what platelet membrane glycoprotein(s)?
- Bernard-Soulier syndrome
- autosomal recessive
- GP Ib
- What syndrome describes a defect in platelet aggregation?
- How is this inherited?
- There is a defect in what platelet membrane glycoprotein(s)?
- Glanzmann thrombasthenia
- autosomal recessive
- GP IIb and IIIa
In Glanzmann thrombasthenia, there is no (…) linking of platelets and there is easy bleeding and no (…)
- fibrinogen linking
- no clot retraction
What is the platelet count levels and size of platelets in Glanzmann thrombasthenia?
both are normal
What is the platelet count levels and size of platelets in BSS?
- low platelet count
- giant platelets
What is the differential diagnosis for seeing giant platelets?
- ITP
- BSS
If platelet counts are normal and there are found to be platelets in clumps, what is the differential diagnosis or likely diagnosis?
VWD
Pertaining to Glanzmann thrombasthenia:
- There is a glycoprotien (…) deficiency
- This causes problems with platelet (…)
- What clinical manifestations are common?
- What is the platelet count/size?
- There will be a (…) platelet response and (…) to ADP and collagen
- What will the platelet response be to risocetin?
- There will be a decreased expression of GP IIb/IIIa on (…)
- IIb/IIIa deficiency
- aggregation
- mucosal bleeding, easy bruisability
- normal platelet count/size
- abnormal platelet response and aggregation to ADP/collagen
- normal platelet response
- flow cytometry
Pertaining to Bernard Soulier syndrome:
- This is a platelet (…) defect
- (…) is missing and cannot attach to complex
- What clinical manifestations are common?
- There will be a (…) platelet test - risocetin
- There will be a (…) response to ADP and collagen
- adhesion defect
- GP Ib
- mucosal bleeding
- abnormal platelet test
- normal response to ADP/collagen
What is the classic triad for bernard soulier syndrome?
- thrombocytopenia
- prolonged bleeding time
- giant platelets on peripheral smear
What is the treatment for Bernard Soulier Syndrome?
- platelet transfusion
- DDAVP (decrease bleeding time)
- antifibrinolytics (tranexamic acid) - pt should have access to drug at home
What is used for acute bleeding when it is not stopping?
tranexamic acid (antifibrinolytics)
What is the treatment for Glanzmann thrombasthenia?
- platelet transfusion
- local hemostatic agents
- antifibrinolytics (tranexamic acid) - pts should have access to drug at home
