3.3b RBC: Bleeding Disorders Flashcards
Functions of platelets (3)
Adhesion
Aggregation
Degranulation/Release Reaction
Note: any abnormality in those three will affect bleeding time
What labs determine PLATELET NUMBER and FUNCTION
Bleeding Time
Bleeding disorders (5)
- Vessel wall abnormalities
- Abnormalities in platelet number
- Abnormalities in platelet function
- Abnormalities in clotting factors
- Disseminated Intravascular Coagulation
In clotting factor dysfunction, what factors are involved and what lab parameter is affect?
“WAR-EXPAT”
Warfarin/Coumadin - Extrinsic factors - Affect PT
Other Mnemonics:
- PWET: PT is for Warfarin and Extrinsic pathway
- PHITT: PTT is for Heparin and Intrinsic pathway
- This involves small hemorrhages in the skin or mucous membranes
- Non-thrombocytopenic purpura (no decrease in platelets)
- All bleeding parameters are normal
Vessel Wall Abnormalities
What are the causes of vessel wall abnormalities? (5)
- Infection with rashes
- Meningococcemia
- Measles
- Infective endocarditis - Decreased collagen
- Scurvy
- Ehlers Danlos - Drugs
- PCN
- Sulfa drugs - Henoch Schonlein Purpura
- Immune complexes circulating in blood attack blood vessels - Hemorrhagic Telangiectasia
- aka Weber-Osler-Rendu Syndrome
Bleeding disorder involving hemorrhages in skin and mucous membranes, GI, GU, easy bruisability
Abnormalities in platelet number (thrombocytopenia)
One of the complications of thrombocytopenia
Intracranial bleeding (usually the cause of death in adults)
What is the picture of PT and PTT in bleeding that results from thrombocytopenia?
Normal
What are the causes of Abnormalities in platelet number? (5)
- BM disease (decreased platelet production)
- Infective megakaryopoiesis (B12 deficiency)
- Increased destruction (decreased platelet survivial)
- Massive transfusion (plasma volume and red cell mass are reconstituted but number of circulating platelets is reduced)
- Sequestration (thrombocytopenia may develop in patients with splenomegaly)
What are examples of BM diseases that decreased platelet production? (2)
- Aplastic anemia
2. Myelopthisic anemia
Infective megakaryopoiesis results from deficiency in?
B12
What are the types of Heparin induced thrombocytopenia? (2)
- Type I HIT
2. Type II HIT
The ff describe which type of Heparin Induced Thrombocytopenia (HIT)?
- Thrombocytopenia develops 1-2 DAYS after heparin initiation
- CONTINUE to give heparin
- Mechanism of thrombocytopenia is NON-IMMUNE (it’s due to a DIRECT EFFECT of HEPARIN on platelet activation)
Type I HIT
The ff describe which type of Heparin Induced Thrombocytopenia (HIT)?
- Thrombocytopenia occurs 1-2 WEEKS
- IMMUNE-MEDIATED (body develops Ab against platelets) :. must STOP heparin because it will continue to destroy platelets –> bleeding
Type II HIT
The ff describes which cause of thrombocytopenia?
- Plasma volume and red cell mass are reconstituted but number of circulating platelets is reduced
- Throbocytopenia occurs because whole/packed blood that comes from the fridge ha no functional platelets
- Produces DILUTIONAL THROMBOCYTOPENIA
Massive Transfusion
What diseases are associated with abnormalities in platelet number? (2)
- Idiopathic Thrombocytopenic Purpura (ITP)
2. Thrombotic Thrombocytopenic Purpura (TTP)
The ff describes which disease associated which abnormality in platelet number?
- Autoimmune disease: Ab vs. platelets
- BM: normal or with increased megakaryocytes
- Steroids are given
- Platelet concentrates are a contraindication
Idiopathic Thrombocytopenic Purpura (ITP)
What are the types of ITP? (2)
- Acute ITP
2. Chronic ITP
Which type of ITP is being described?
1. Caused by autoAb against platelets
2. A self-limited disorder in CHILDREN following viral infection for 1-2weeks
3, Usually resolves spontaneously within 6 months
Acute ITP
Which type of ITP is being described?
- Caused by autoAb against platelets (specifically, their membrane glycoproteins: IIb-IIIa or Ib-IX)
- In majority of cases, anti-platelet Ab seen is IgG
- Seen in ADULTS, especially reproductive females with autoimmune disorders or lymphoproliferative disease
- An alternative treatment to steroids is removal of spleen
Chronic ITP
What is the pathogenesis of Chronic ITP?
Antiplatelet Ab act as opsonins (recognized by IgG Fc receptors) –> increased platelet destruction
Like in autoimmune hemolytic anemia
In TTP, autoAb are directed against which membrane glycoprotein?
IIb-IIIa or Ib-IX
The ff describes which disease associated which abnormality in platelet number?
1. It is characterized by MICROANGIOPATHIC hemolytic anemia, fever, transient neurologic deficits, renal failure, thrombocytopenia, usually in the 4th decade of life
TTP
What is the morphology seen in chronic TTP
Widespread hyaline membrane microthrombi
What is the pathogenesis in TTP?
Excessive activation of platelets (due to deficiency of enzyme)
Which enzyme is deficient in TTP?
ADAMTS13/vWF protease
What happens when there is deficiency in ADAMTS13/vWF protease?
Accumulation of vWF in blood vessel –> stimulates adhesion, aggregation, thrombosis
What are the functions of vWF? (2)
- Protects Factor VIII
2. Helps in platelet adhesion
What is the end results of TTP?
Microthrombi in different parts of the body
Treatment of TTP
Plasma exchange
What is a differential diagnosis of TTP?
Hemolytic Uremic Syndrome (HUS)
What similarity (1) and difference (1) does TTP and HUS have?
Similar: Microthrombi everywhere
Difference lies in etiology
- (HUS) E.coli secondary to gastroenteric effect –> Shigella-like toxin that will cause thrombosis
- (HUS) No neurologic deficits
- (HUS) Medical emergency that needs immediate plasma transfusion
Examples of INBORN abnormalities in platelet function (3)
- Von Willebrand Disease
- Bernard Soulier Disease
3 Glanzmann Thrombasthenia
Pathogenesis of Von Willebrand Disease
Defective ADHESION due to deficient vWF (needed for platelet function and Factor VIII stability)
The ff are s/sx of which inborn abnormality of platelet function?
- Spontaneous bleeding from mucous membrane
- Excessive bleeding from wounds
- Menorrhagia
- Hemarthrosis
Von Willebrand Disease
What would the ff lab parameters look like in Von Willebrand Disease?
- BT
- aPTT
- Ristocetin Aggregation Test
- Increased BT
- Increased aPTT
- Reduced rostocetin aggregation test
- NORMAL PLATELET COUNT
In Bernard Soulier Disease, there is defective adhesion due to absence of?
Glycoprotein Ib
In Glanzmann Thrombasthenia, there is deficient AGGREGATION due to the absence of? (2)
- Glycoprotein IIb and IIIa
Acquired abnormalities in platelet function may be caused by? (2)
- Aspirin/NSAIDs (inhibit COX, suppresses PG)
2. Uremia
Deficiency in which factors result to abnormalities of clotting factors? (3)
- Factor VIII - Hemophilia
- Factor IX - Christmas disease/Hemophilia B
- Factor II, VII, IX, X - Liver disease/Vitamin K Deficiency
In abnormalities in clotting factors, what do the ff labs look like?
- Platelet count
- BT
- CT
- PT
- aPTT
- Normal platelet count
- Normal BT
- Increased CT
- Increased PT
(involves extrinsic and common factors: Factors VII, I, II, V, X) - Increased aPTT
(involves extrinsic and common factors)
It is an acute, subacute, or chronic thrombo-hemorrhagic disorder occurring as a complication in a variety of diseases
aka Consumption Coagulopathy
Disseminated Intravascular Coagulation (DIC)
What is the morphology seen in DIC?
Microthrombi
What is the lab diagnosis in Acute DIC?
All parameters are ABNORMAL:
- Decreased platelet
- Increase in everything else
What is the lab diagnosis in Chronic DIC?
(+) D-dimers and fibrin split products
What are the clinical syndromes associated with bleeding? (2)
- Waterhouse-Friedrichsen Syndrome
- Meningococcemia –> Adrenal hemorrhage - Sheehan’s Postpartum Necrosis
- Pituitary necrosis after complicated delivery
