Hematology 3 - Hemostasis Vol. III

omarys's version from 2017-10-07 20:20

Section 1: megakaryopoiesis & thrombopoiesis

Question Answer
thrombopoiesisthrombocyte generation. Thromobocytes (=platelets) are ligations of the cytoplasm from megakaryocytes
Dense granules containADP (& other platelet agonists)
Alpha granules containAdhesion, growth and clotting factors
Normally ____ of platelets are in the spleen; any more than that and we're talkin problems.1/3rd
The replication of chromosomes in the absence of cell or nuclear division, resulting in numerous copies within each cellendomitosis
Which cells undergo endomitosis?Megakaryocytes
What induces differentiation into MK?TPO
TPO also inducesproduction of thrombocytes from MK's
Hemostasis has these stages:initiation (inc' adhesion, activation, degran', aggregation) > propagation (proteins) > termination > degradation of clot (> wound healing)
Examples of subendothelial molecules that platelets bind in the adhesion phase?Laminin, fibronectin, collagen, vWF
The activation phase involves several ___, e.g.-agonists ; ADP, thrombin, TXA2, collagen
What is secreted upon degranulation?ADP, thrombin, TXA2 (all agonists)
What important receptor is active in the aggregation phase?GPIIB-IIIA (aggregation happens thru fibrinogen or vWF)
vWF is also the ___ of factor ___.carrier ; 8

Section 2: Medications and tests

Question Answer
Aspirin inhibits the enzymeCOX (no TXA2 which is an important agonist- but there're others)
Clopidogrel (AKA ____) blocks-Plavix ; the ADP receptor (oft' administered alongside aspirin after MI)
Examples of GPIIb-IIIa blockers?TIROfiban, abcIXImab, eptiFIBAtide (COMPLETE prevention of aggregation)
Best test for platelet functionality?platelet aggregation test (slow centrifugation of blood > add agonist (ADP/collagen/AA) > solution should be clear if aggregation is OK)
Glanzmann's?thrombasthenia, defective or low levels of GPIIB-IIIA (AR inheritance)
GPIIB-IIIA is the receptor forfibrinogen
Ristocetincan induce platelet aggregation thru vWF (so some aggregation will still occur in Glanzmann's)
In vWF diseasesall agonists may facilitate aggregation (cuz they work thru GPIIBIIIA) except ristocetin

Section 3:

Question Answer
Myeloproliferative diseases like _____ primarily affect the (arteries/veins?).thrombocytosis ; arteries
Hypercoagulability due to platelet abnormalities is usually inthe arterial system (MI, CVA)(whereas DVTs and PEs are due to coagulation FACTOR (protein) abnormalities)
White vs. red thrombiwhite are in arteries (platelets) ; red are in veins (RBCs get stuck in fibrin mesh)
Normal platelet count150-450K / μL (i.e. 150 million per mL)
What must be done/analyzed in a bleeding patient or a patient w thrombocytopenia?blood smear (to visualize platelets & validate their deficiency)
Surgical bleeding occurswhen platelet count is below 50K
Spontaneous bleeding occurswhen platelet count is very low- 10-20K
Cerebral bleeding occurswhen platelet count is < 5K
Typical bleeding pattern in platelet diseasesin skin and mucosa (rarely into muscles or joints)
Typical bleeding pattern in coag' factor diseasesdeep tissues, e.g. muscles/joints

Section 4: Diseases I (thrombocytopathies)

Question Answer
What is normal in Glanzzman's thromboasthenia?Platelet count, PT, PTT (cuz problem is platelet aggregation, so there'll be bleeding in skin and mucosa anyway)
An AR coagulopathy characterized by deficiency in GP-IB; AKA hemorrhagiparous thrombocytic dystrophyBernard-Soulier syndrome (BSS)
Deficiency or malfunction of GPIIB-IIIAGlanzmann's thromboasthenia
The most common hereditary blood-clotting disorder in humans; characterized by compromised quality or quantity of ___Von-Willebrand disease ; vWF
Other diseases that might compromise platelet function due to lack of platelet (dense) granulesSPD (storage pool diseases)

Section 5: Diseases II (thrombocytopenia - possible causes or risk factors)

Question Answer
(1) Pseudothrombocytopeniadue to clumping of platelets in test tube, or to satellism (round WBCs) - these platelets aren't counted
(2) Splenic sequestration is anacute condition of intrasplenic pooling of large amounts of blood due to splenomegaly (& up to 80% of platelets will pool there)
(3) reduced production of platelets might be due toVery Destroyed Thrombocytes BoneMarrow is a Cunt (viral infections, diet, toxic injury, BM has metastases or has failed (MDS), congenital disease like Bernard-Soulier)
Insufficient consumption of B12 or folic acid (=D in VDTBMC) will also lead toother cytopenias
(4) increased elimination of platelets might be due toA. immune stuff: ITP (immune thrombocytopenic purpura) including TTP ; B. non-immune: TMA (thrombotic microangiopathies) inc' DIC, TTP, HUS
Der 5th pillarthe pregz (affects more than just platelets)
(6) massive bleeding that's rectified using plasma and blood only (no platelets)hemodilution

Section 5.5: Thrombocytopenias - TMAs

Question Answer
Clotting tests show normal results inHUS
Examples of thrombotic microangiopathies?Thrombotic thrombocytopenic purpura ; Hemolytic-uremic syndrome ; Disseminated intravascular coagulation
In TMAs,clots form in small blood vessels (--> taking up platelets > thrombocytopenia) and this hinders RBC passage thru the vessels and leads to their hemolysis
TTP can becongenital or acquired (the latter is usually idiopathic/AB's against ADAMTS13; seen in HIV+, transplant patients, cancer patients)
In congenital TTP, ADAMTS13 does notcleave circulating vWF multimers >> platelets aggregate >> blood vessels blocked & thrombocytopenia
Tx of acquired TTP?plasmapheresis (for AB) and fix ADAMTS13 levels ('adjuvant' tx: folic acid, anti-platelets, steroids, RITUXIMAB (anti-CD20)
_________% of patients survive with proper tx of TTP (10% will survive w/o tx)90
The clinical presentation of TTP in 40% of patients is a pentade:fever, pre-renal failure, neurological symptoms (brain blood vessels blocked), thrombocytopenia & bleeding risk (but clotting tests NORMAL), hemolytic anemia (rise in LDH due to hemolysis and tissue damage)
In both HUS and DIC, cell ___ can be seen.debris

Section 5.75: Thrombocytopenias - ITP

Question Answer
ITP is usually transient in _____ but not in _____.children ; adults
Pathogenesis in ITP involvesAB's against MK and platelets >> AB-covered platelets get broken down in spleen (there's also dysregulation of T cells)
Tx of ITPTPO agonists (induce BM to produce more MKs/platelets)
Most cases of ITP are _____ but some can be secondary to-idiopathic ; lupus, APLA, CLL, Evan's syndrome (AIHA + immune thrombocytopenia), HIV, HCV, H. pylori
The clinical presentation of patients is a function of theirplatelet count (over 50K is usually asymptomatic; under 10 is risk of major bleeding)
Dx of ITP?eliminate other causes cuz spleen size is normal and patients are usually asymptomatic!
(0) lab tests: in a blood test, there will bethrombocytopenia only (other cell counts OK), sometimes iron def (due to menorrhagia)
(0) Clotting function tests in ITP?normal mostly
(0) blood smear will showfew (large) platelets (other cell #s OK)
(0) The BM in ITP will havenormal-high MKs, CELLULARITY OK (unlike MDS or leukemia)

Section 5.8: ITP treatment

Question Answer
The purpose of tx in ITP is to preventbleeding
1st line:high doses of steroids, IVIG to occupy Mφ in spleen (latter is more for emergency)
2nd line:splenectomy (70% of adults will completely heal after this - but side effects, increased risks sepsis)
3rd line isrituximab (30% of patients responsive)
final tx option:TPO agonists (most patients responsive)

Section 6: Other

Question Answer
While RBCs travel at the centre of the blood vessel, platelets-are pushed to the periphery, such that they're close to the site of injury should it happen
Platelets might have a certain degree ofprotein synthesis (they contain RNA)
Activated platelets havefilopodia (microspikes)
For platelets to adhere to vWF, there is usually supposed to behigh shear stress - rapid flow (arterial blood)
Collagen is more relevant in these conditions:slower flow speed (veins)
Where's vWF?at the subendothelium (insoluble) or secreted from platelets (alpha gran') or endoth. cells (soluble)
3 functions of vWFadhesion of platelets (thru GP-IB-IX-V) ; aggregation of platelets (like fibrinogen) ; carrier of factor 8 (so low vWF --> lower factor 8 levels)
Excess vWF is involved inTTP
The most abundant receptor on platelets isGPIIb-IIIa (whose activation is the purpose of the whole activation process)
In aggregation, the bridge bwn platelets isfibrinogen (binds GPIIb-IIIa) or vWF
While aspirin is used as a tx for hypercoagulability due to platelet dysfunction, ____ and clexane are used for hypercoagulability in the venous system (might be relevant in e.g. PE).coumadin
Myeloproliferative diseases (e.g. polycythemia vera, essential thrombocytosis) are tx'ed with -aspirin
white thrombi:antiplatelet txred thrombi:anticoagulation tx
Thrombocytopenia is when platelet count is< 150 million / mL
How to assess platelet count using blood smearuse 100x magn' > count platelets > multiply by 10-20K
First presentation when there's spontaneous bleeding (plt # is <10 million/mL) isdry purpura (skin bleeding; usually in lower limbs)
Vasculitis vs. bleedingpurpura in former is palpable
Wet purpura is when there's -mucosal bleeding (pretty serious)
Collagen receptor isGPIa-IIa
DIC vs Glanzmann'sin DIC tests will be abnormal (PT, PTT) due to consumption of coag' factors
The platelet aggreg' test (using the aggregometer), the gold standard for platelet function, can not only indicate if there's platelet dysfunction but also -which aggreg' pathway is involved (a different agonist is added each time)