12 - Bleeding Disorders and Thrombocytopenia Flashcards
What hematologic condition is most associated with petechiae?
Thrombocytopenia! (Ecchymosis is more common with platelet dysfunction)
Your patient has the following lab results and peripheral blood smear. What is the primary defect in hemostasis in this patient?
Defect in platelet number.
What is immune thrombocytopenia (ITP)? How is it diagnosed?
Can be primary (no identified cause) or secondary (identified cause, such as underlying disease or drug exposure).
Disagnosed by measurement of platelet levels (<100 x 10^9/L) and exclusion fo non-autoimmune causes of thrombocytopenia.
- response to therapy is hte most compelling diagnostic evidence
- platelet-bound or circulating auto-Ab against platelet antigens found in ~60% of pts
How does immune thrombocytopenia usually present clinically?
- Petechiae and ecchymoses
- Spontaneous bleeding is uncommon when the platelet count is >20 x10^9 /L^2
- Bleeding episodes, most commonly mucocutaneous
- Intracranial hemorrhage and other major internal bleeding is rare
How does immune thrombocytopenia impact children? How does it compare to adult ITP?
Children may be affected at any age, but peak incidence is in early childhood (1-6 yo)
In contrast to adult ITP, pediatric ITP is more likely due to viral illness and usually resolved spontaneously without treatment.
- ~25% of childhood ITP becomes chronic
What are 4 immune modulation therapies that can be used to treat immune thrombocytopenia (ITP)?
- Corticosteroids including dexamethosone or prednisone.
- IVIg
- Splenectomy
- Rituximab
What are 2 platelet related therapies that can be used to treat immune thrombocytopenia (ITP)?
Increased platelet production via thrombopoietin agonists:
- Eltrombopag
- Romiplostim
What is DIC?
An acquired syndrome characterized by systemic intravascular coagulation.
Coagulation is always the initial event, typically followed by bleeding (consuptive coagulopathy)
What are the conditions associated with DIC?
There’s a LOT.
What does laboratory evaulation of DIC include (ie what tests are done and what are the results of those tests) - there are 4?
- Prolonged clotting times (PT, PTT, thrombin time)
- Decreased factor activities
- Elevated D-dimer
- Sometimes thrombocytopenia and hemolytic anemia.
DIC is associated with __________ __________ and __________. Bleeding complications are common.
Microvascular infarction and hemorrhage.
What organs, other than the vasculature, can be involved in DIC?
- Liver
- Kidneys
- CNS
What is the primary treatment of DIC?
It involves correction of the underlying cause of the disease.
Other supportive therapies include the replacement of clotting factors through the use of blood product transfusion (fresh frozen plasma, cryoprecipitate, and platelets).
What is hemophilia?
An inherited bleeding disorder in which there’s a deficiency or lack of:
Factor VIII (hemophilia A)
Factor IX (hemophilia B)
or
Factor XI (hemophilia C)
How would you treat hemophilia?
Treatment requires replacement of the deficient clotting factor, most commonly with recombinant or plasma-derived clotting factors.
How are hemophilia A and B inherited? How does severity levels vary in families? How is Hemophilia C inherited?
Types A and B are X-linked recessive therefore it’s typically expressed in males and carried by females.
Severity level is consistent between family members.
Hemophilia C (factor XI deficiency) is an autosomal disorer affecting men and women equally.
~30% of cases of hemophilia are _____ _______.
New mutations.
What is the incidence and severity of hemophilia A in the US?
20.6 per 100,000 males.
Severe in 50-60%.
What is the incidence and severity of hemophilia B in the US?
5.3 per 100,000 males.
Severe in 44%
What population is hemophilia C most commonly identified in?
Ashkenazi Jews, with homozygosity in 0.2-0.5%
What are some (5) types of bleeds seen with secondary hemostasis?
- Joint bleeding (hemarthrosis)
- Muscle hemorrhage
- Soft tissue
- Life-threatening bleeding (intracranial, neck, ileopsoas, or retroperitoneal
- Other-surgery
A 2 day old male has bleeding from a circumcision. The site has bled for over 10 hours. The lab results are displayed below. What test would you order?
A plasma 1:1 mixing study.
A 2 day old male has bleeding from a circumcision. The site has bled for over 10 hours. A PTT 1:1 mixing test with normal plasma is performed. The PTT decreases from 80 to 28 seconds (normal 24-34s). What is a likely diagnosis?
Hemophilia.
Describe the synthesis and storage of Von Willebrand Factor?
Synthesis: endothelial cells, megakaryocytes
Storage: endothelial cells, alpha granules in platelets
What do levels of vWF vary with (3 things)?
Age: increases with age
Race: 15% higher in blacks
Blood group: 30% lower in group “O”
What are 5 transient things that increase vWF? What decreases it?
Increase:
- sympathetic stimulation
- surgery
- trauma
- exercise
- pregnancy
Decrease: hypothyroidism
What is the function of vWF? How common is von willebrand disease (VWD)?
Function of vWF: adhesion of platelets at site of injury and binds/”protects” factor VIII in the circulation.
VWD is the most common inherited bleeding disorder. Incidence is 0.1-1%.
What are clinical symptoms (4) associated with VWD?
- Mucosal bleeding, especially epistaxis (nose bleeds) and menorrhagia
- Post-op bleeding
- Bleeding from oral cavity
- GI bleeding
What are two ways to treat VWD?
DDAVP (desmopressin acetate): a synthetic analogue of vasopressin that releases VWF from endothelial storage
Transfusion therapy: viral inactivated VWF-FVIII concentrate or cryoprecipitate (in emergency if nothing else available).
How do people get VWD? What is it?
It’s a congenital, inherited disorder that resultsin impaired primary hemostasis (mucocutaneous bleeding).
Bleeding disorders are a common contributor to _______ _______ ______ in menstruating females.
Iron-deficiency anemia
Von willebrand factor protects factor ______ from proteolysis, and factor ____ activity is often dereased in vW disease.
Factor VIII
