Heme Flashcards
From what 2 places is vWF derived?
- Weibel-Palade bodies of endothelial cells
2. α-granules of platelets
___a___ binds sub-endothelial collagen when it is exposed from damage to the endothelial cell wall.
Platelets then bind to its ___b___ receptors to begin the formation of a blood clot.
c) This adhesion of platelets induces a shape change, causing them to degranulate, releasing what 2 mediators?
What are the functions of these 2 mediators?
a) vWF
b) GP1b
c)
1. ADP (dense granules) promotes exposure of GPIIb/IIIa receptors on platelets (for further aggregation)
2. TXA2 promotes platelet aggregation & vasoconstriction
Platelets aggregate amongst each other via linking molecule, __a__, binding to their __b__ receptors, forming a weak platelet plug.
a) Fibrinogen
b) GPIIb/IIIa
Disorders of Primary Hemostasis primarily present w/ what types of symptoms?
Skin & Mucosal Bleeding
- also easy bruising
(i.e. Epistaxis, hemoptysis, GI bleeding, hematuria, menorrhagia)
(intracranial bleeding occurs w/ severe thrombocytopenia)
Intracranial bleeding occurs under what pathologic conditions of primary hemostasis?
When there is Severe Thrombocytopenia
Sizes of the 3 types of skin bleeding?
- Petechiae = pinpoint bleeding
(usually only occurs w/ thrombocytopenia, not qualitative disorders) - Purpura = >3mm
- Ecchymoses = > 1cm
What is the most common cause of Thrombocytopenia in children & adults?
ITP
Idiopathic/Immune Thrombocytopenic Purpura
ITP - pathology?
- Autoimmune production of IgG antibodies against platelet antigens (ex: GPIIb/IIIa)
- Antibodies are produced by the spleen & antibody-bound platelets are consumed by splenic macrophages
ITP - Prognosis?
- Acute form is usually seen in children & is self-limited & usually resolves w/in a few weeks
- Chronic form usually arises in adults (women of child-bearing age), lasts a bit longer, & may cause short-lived thrombocytopenia in offspring (IgG can cross placenta)
How is PT/PTT affected in Thrombocytopenia?
They are Normal
- these reflect the coagulation cascade, not platelet count (which is primary hemostasis)
ITP - Laboratory Findings?
- ↓ Platelet count (<50 K/μL)
- Normal PT/PTT
- ↑ Megakaryocytes on bone marrow biopsy
ITP - Tx?
Corticosteroids
- IVIG if bleeding (distracts splenic macrophages)
- Splenectomy (refractory cases, last option)
Microangiopathic Hemolytic Anemia - pathology?
Pathologic formation of platelet micro thrombi in small vessels
- shear RBCs as they squeeze by in small vessels
- uses up platelets → thrombocytopenia
- Seen in TTP & HUS
Thrombotic Thrombocytopenic Purpura (TTP) - pathology?
- ↓ADAMS TS13 (enzyme), which normally chops up vWF multimers for degradation
- Leads to abnormal platelet adhesion & micro thrombi formation → ITP
- Usually seen in adult female w/ acquired autoimmune degradation of ADAMS TS13
2 pathologies that lead to Microangiopathic Hemolytic Anemia?
Thrombotic Thrombocytopenic Purpura
&
Hemolytic Uremic Syndrome
HUS - pathology?
- E. coli 0157:H7 produces E. coli verotoxin, which damages endothelial cells →platelet micro thrombi (in kidneys & brain) → Hemolysis → Thrombocytopenia
- Children get it from undercooked beef
HUS - Clinical symptoms?
- Skin & mucosal bleeding
- Microangiopathic Hemolytic Anemia
- Fever
- Renal insufficiency
- CNS abnormalities
**Same as TTP
TTP - Clinical symptoms?
- Skin & mucosal bleeding
- Microangiopathic Hemolytic Anemia
- Fever
- Renal insufficiency
- CNS abnormalities
**Same as HUS
TTP - TX?
Plasmapheresis (remove proteins, autoantibodies, from blood)
- Corticosteroids
Abnormal Thrombin time - means what?
Fibrinogen Deficiency
DIC
In Thrombocytopenia, how do you differentiate between decreased production & increased destruction of platelets?
↓ production = ↓Megakaryocytes in bone marrow
↑ destruction = ↑Megakaryocytes in bone marrow
Hemophilia A - lab findings?
- ↑aPTT
- Factor XIII assay (confirmatory)
(Normal BT, PC, PT, TT)
Hemophilia B - lab findings?
- ↑aPTT
- Factor IX assay (confirmatory)
(Normal BT, PC, PT, TT)
von Willebrand disease - lab findings?
- ↑aPTT, ↑ Bleeding time
- vWF assay (confirmatory)
(Normal PC, PT, TT)
DIC - lab findings?
- ↑ BT, PT, aPTT, & TT
- ↓ Platelet count
- Fibrin & fibrinogen degradation products
What molecule links platelets via binding G2b/3a receptors?
Fibrinogen
Abnormal Ristocetin test means what?
vWF deficiency (diminished aggregation)
OR
Bernard-Soulier Disease; ↓ G1b receptors (no agglutination)
Clopidogrel - MOA?
Inhibits the release of ADP from platelets, thus inhibiting platelet expression of G2b/3a receptors
(ADP normally stimulates expression of G2b/3a receptors)
Ticlodipine - MOA?
Inhibits the release of ADP from platelets, thus inhibiting platelet expression of G2b/3a receptors
(ADP normally stimulates expression of G2b/3a receptors)
(same as Clopidogrel)
Abciximab - MOA?
Interferes w/ G2b/3a function
normal function = binding to fibrinogen to bind platelets together
Normal function of ADAMSTS13?
Cleaves large multimers of vWF that are released from Weibel-Palade bodies into smaller multimers & monomeric units.
The large & ultra-large multimers that are originally released are VERY adhesive & reactive, so they should be broken down upon release.
Prostacyclin (PGI2) function in the coagulation cascade?
Prostacyclin is a potent inhibitor of platelet aggregation & prevents their deposition on normal vascular endothelium.
It is synthesized by endothelial cells when cAMP levels increase (whereas TXA2 causes ↓cAMP)
What is Christmas Disease?
Hemophilia B (↓ factor IX)
- indistinguishable from Hemophilia A, just less common
Vitamin K deficiency - heme lab findings?
↑ PT & aPTT
Classic pentad of TTP?
Fever, Microangiopathic hemolytic anemia, Thrombocytopenia, Renal insufficiency, & Neurologic abnormalities
Dx?
- Primary hemostatic bleeding w/ gingival hemorrhages
- Bleeding into muscles & subcutaneous tissues
- Hemorrhagic perifollicular hyperkeratotic papules, each papule surrounding a twisting, corkscrew-like hair
Scurvy (vitamin C deficiency)
- also associated w/ a “tea & toast” diet
