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HOPE
Maram Al-anbar
9 - 9 - 2014
Maram Alanbar Bleeding Disorders Hope / 2010
^^ Attention Please ^^
We ( correction team of pediatric package^HOPE/2010^ ) had decided
to make one lecture of bleeding disorders in place of the two lectures
we had in our package Including the content of the previous lectures
Plus other sources to make it one organized lec. Hoping for you to get
the most benefit ,, study easily ,, and not getting distracted or
bothering yourself looking at other sources
the sources of this lecture are : “ Previous 2 lectures + Nelson +
Pediatric in Page + some youtube videos “ ...
** NORMAL HOMEOSTASIS **
it’s a dynamic process that occur in area of VASCULAR INJURY
composed of ::
*platelets *vascular wall *procoagulant proteins * anticoagulant
proteins
Now .. What is the sequence of events that occur in this process ?!!
Once there is injury to the vascular endothelium what happens ?? ::
1* Vasoconstriction ..
2* Primary Homeostatic mechanism (platelet plug formation) ..
3* Secondary Homeostatic mechanism (fibrin clot ,, thrombus) ..
4* Anti thrombotic and Fibrinolytic events ..
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Maram Alanbar Bleeding Disorders Hope / 2010
forming in the end Primary Homeostatic Plug ( Platelet Plug ) that will
temporally stop the bleeding ,,
Soo ...
**Adhesion is : Platelet - Subendothelial Interaction (GP-Ib _vWF)
**Aggregation is : Platelet - Platelet Interaction ( GPIIb/IIIa _
fibrinogen_GPIIb/IIIa )
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Maram Alanbar Bleeding Disorders Hope / 2010
** EXTRINSIC ** ** INTRINSIC **
Shorter pathway .. Longer pathway ..
Starts with factor 7 .. Starts with factor 12 ..
Stimulated with tissue Stimulated with inflammatory
factor as a result of mediator as a result of
trauma to the vessel .. inflammation ..
The pathway is 7 10* 12 11 9(in presence of
activated F8 + Ca + PF) 10*
*At F10 starts the common
pathway 10(in presence of 2 1 details below
activated F5 + Ca + PF)
WARFARIN can block this HEPARIN can block this
pathway (inhibiting the pathway (stimulating
production of vit.k antithrombine III that inhibits
dependent factors thrombin(F2) & factors
-10,9,7,2- by inhibiting the -11,10,9- ..
activation of vit.k ..
Measured by PT/ INR Measured by aPTT test ..
tests ..
Cascade means in a step wise manner where the active form of the
factor acts as an Enzyme ,, where as the inactive form acts as a
Substrate Ex. FXIIa act as an enzyme ,, FXI act as a substrate ...
أفضل تعريف لذاتك أنك لست أفضل من أحد ولست كأي أحد ولست أق ل
... من أحد
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Maram Alanbar Bleeding Disorders Hope / 2010
I Ia
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Maram Alanbar Bleeding Disorders Hope / 2010
Now let’s talk about thrombin and the imp. Functions that performs ::
1* conversion of fibrinogen into FIBRIN ..
2* activation of FXIII( fibrin stabilizing factor ) that will bind fibrin
and stabilize it into a CLOT ..
3* act as platelet AGONIST ( attracts more and more platelets ) ..
4* activates plasminogen into PLASMIN ( which is fibrinolytic
enzyme )
5* activates factors V , VIII , XI ..
** Imp Note “” all coagulation factors are made in the liver except
FVIII made in vascular endothelium and bound with vWF “”
** another Note :
“” Deficiency of FVIII , FIX lead to sever bleeding disorder “”
“” Deficiency of FXI lead to mild bleeding disorder “”
“” Deficiency of FXII is asymptomatic “”
AND the last stage after the thrombus(clot) has been formed and the
bleeding has been stopped now we want to :
** prevent further thrombotic events by anti thrombotic enzymes ex.
Anti-thrombin III ,, protein C ,, protein S ...
** Dissolve the thrombus and resume the blood flow by fibrinolytic
enzymes ex. Plasmin ..
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Maram Alanbar Bleeding Disorders Hope / 2010
:: BLEEDING DISORDERS ::
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Maram Alanbar Bleeding Disorders Hope / 2010
Platelets disorders
** Sequestration :Hypersplenism ..
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Maram Alanbar Bleeding Disorders Hope / 2010
ITP
>> I stands for :
**Idiopathic ( unknown reason )
**Immune ( involvement of auto antibodies)
**Isolated ( cuz only Thrombocytopenia is present No Anemia ,, No
Leukopenia )
>> T stands for Thrombocytopenic ( cuz it’s quantitative disorder with
low platelet count )
>> P stands for Purpura ( cuz the usual presentation is purpuric rash )
Etiology
>> it’s thought to be auto immune with auto antibodies ( IgG , IgM )
that bind with platelet membrane ,, signaling them for destruction by
macrophages in Spleen ..
>> it affects young children more likely ..
>> can be divided into *Acute ( last < 6 months ,, affect young children )
and *Chronic (last > 6 months,, affect young adults mainly females )..
Clinical
presentation
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Maram Alanbar Bleeding Disorders Hope / 2010
Therapy
>> therapy doesn’t affect long term outcome of ITP but rather
increase plt count in acute conditions ..
>> not necessary if plt count >30,000
>> if <30,000 it depends on severity of symptoms ::
1* IVIG ( it has the same effect of steroids but with rapid action >> WE
start with it , if it doesn’t work start steroids )
2* Corticosteroids ( before using it U should do BM biopsy to exclude
malignancy ex. Leukemia cuz steroids are contraindicated in leukemic
patients )
3* anti-RhD Ig ( for Rh +ve )
these 3 ways can decrease rate of clearance of sensitized platelets
rather than decreases antibodies production ...
4* Platelets transfusion ( not preferred cuz ITP is autoimmune so Abs
can attack the transfused platelets ) used only in sever plt reduction ...
5* Splenectomy used in *chronic type ,, and *acute type only with life
threatening bleeding ( it should be the last modality if previous ways
didn’t work )
>> 80% resolve in 6 months ..
>> 1% can develop Intra Cranial Hemorrhage ICH ..
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Maram Alanbar Bleeding Disorders Hope / 2010
Now this MAHA happens in many conditions like what we’re concerned
with now >> HUS ,, TTP ,, DIC << ..
HUS
** H stands for Hemolytic ( hemolytic anemia which is characterized
by schistocytes <fragmented RBCs> in Blood film ) ..
** U stands for Uremic ( uremia due to acute renal failure that occurs
bcz of renal vessels being affected ) ..
** S stands for Syndrome ..
Etiology
>> 90% are caused by E.coli O157:H7 that produces verotoxin which
attacks the endothelial lining of renal vessel leading to MAHA ..
>> Childhood disease ..
Clinical
presentation
Tests
>> CBC :: platelets ,, Hb ..
>> Blood film :: schistocytes ..
>> their may be Hematuria ,, Proteinuria ..
Therapy
>> often resolves spontaneously ..
>> Dialysis might be needed for ARF ..
>> Plasma exchange in sever persistent disease ..
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Maram Alanbar Bleeding Disorders Hope / 2010
TTP
** Thrombotic Thrombocytopenic Purpura **
Etiology
Clinical
Presentation
>> multiple organs are involved <<
>> Fever ..
>> CNS signs ( seizure ,, altered level of consciousness , ..)
>> signs of renal failure ..
>> superficial bleeding ..
Tests
Therapy
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Maram Alanbar Bleeding Disorders Hope / 2010
DIC
>> this disease is actually both Platelet & Coagulation disorder <<
>> it’s mostly seen in ICU patients ,, usually with shock <<
Etiology
Clinical
Presentation
Tests
>> platelets >> bleeding time >> PT , PTT
>> fibrin degradation products(D-Dimer) ,,>> fibrinogen
Therapy
**Treatment of DIC is challenging ,, what we do is :
1- Treat the underlying cause
2- Replace *Platelets by transfusion
*clotting factors by FFP(fresh frozen plasma )
*Fibrinogen by cryoprecipitate
3- using Heparin for thrombosis is controversial
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Maram Alanbar Bleeding Disorders Hope / 2010
Bernard-soulier (BS)
Glanzmann
Thrombasthenia (GT)
>> NL Platelet count ,, NL Adhesion ,, AbNL AGGREGATION
** aggregation occur when platelets bind with each other via their
receptor GPIIb-IIIa having fibrinogen in between as ligand **
>> here we have deficiency of GPIIb-IIIa ....
von-Willebrand Disease
(vWD)
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Maram Alanbar Bleeding Disorders Hope / 2010
COAGULATION DISORDERS
1- Hemophilia A ,, B
2- DIC
3- vWD
4- Liver Disease
5- Vitamin K Deficiency
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Maram Alanbar Bleeding Disorders Hope / 2010
Hemophilia
Etiology
>> Hereditary Deficiency of pro-coagulant proteins ::
* F VIII in Hemophilia A
* F IX in Hemophilia B
>> both are X-Linked disorders
>> Males are mainly affected 1 : 5000 in A ,, 1 : 25,000 in B
>> Female is usually asymptomatic carrier , unless , her father is
affected and mother is carrier, turner syndrome (XO), or lionization of
chromosome X ..
>> Hemophilia A accounts for 80-85 % of cases
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Maram Alanbar Bleeding Disorders Hope / 2010
Clinical
Presentation
Tests
>> aPTT will be High
>> specific factor assay ( to determine whether F VIII or F IX )
Therapy
*** for << F VIII >> we need 0.5U/Kg to increase the level by 1%
Soo... Dose of F VIII = ( Desired level (%) * weight (kg) * 0.5 )
*** for << F IX >> we need 1.5U/Kg to increase the level by 1%
Soo... Dose of F IX = ( Desired level (%) * weight (kg) * 1.5 )
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