STEP 2

1. How is the meccanism of hemostatis?

- vascular spasm
Damaged or torn blood vessels will undergo vasocontriction so that will slow the flow of blood
out through the wounded area so that blood can be reduced. Then the endothelial layer in the
blood vessels will attach to each other then close the damaged blood vessels.
- platelet formation
Normal circumstances, platelets in circulation are not attached to the endothelium, but if the
endothelial layer is damaged, the platelets will be attached to exposed collagen. After the
platelets collected, it will issue some granules whose content is ADP. ADP will cause the surface
of the passing platelets to become sticky and attached to the platelet collection. Inherent
pltelets and then issue more ADP so as to cause more platelets are approaching and aggregating
so that there is a blood vessel plug that is wound by a platelet collection.
- coagulation factor
The process of transforming blood from the liquid into a semi solid gel. The formation of a blood
clog plug on a platelet plug will srengthen and support the plug and srengthen the patch
covering the defect.

2. What are the components that play a role in hemostatis?

- Endhotelial cells
- Platelets / Trombosit
- Coagulation System

3. What are the caused of hemostatis?

4. What is the function of trombosit in hemostatis?
1. Adhesion
This means binding of platelets to nonendothelial surfaces, particularly subendothelium which
is uncovered following vascular injury. von Willebrand factor (vWF) mediates adhesion of
platelets to subendothelium via GpIb on the surface of platelets (Fig. 1.25). Congenital absence of
glycoprotein receptor GpIb (Bernard-Soulier syndrome) or of von Willebrand factor in plasma
(von Willebrand disease) causes defective platelet adhesion and bleeding disorder.
Platelets normally circulate as round to oval disc-like structures. With activation, platelets undergo
shape change, i.e. they become more spherical and form pseudopodia. This shape change is due to
reorganization of microtubules and contraction of actomyosin of microfilaments.
2. Release reaction (secretion)
Immediately after adhesion and shape change, process of release reaction or secretion begins.
In this process, contents of platelet organelles are released to the exterior. ADP released from
dense granules promotes platelet aggregation. Platelet factor 4 released from alpha granules
neutralises the anticoagulant activity of heparin while platelet-derived growth factor stimulates
proliferation of vascular smooth muscle cells and skin fibroblasts and plays a role in wound
healing.
Activated platelets also synthesise and secrete thromboxane A2 (TxA2). Platelet agonists such
as ADP, epinephrine, and low-dose thrombin bind to their specific receptors on platelet surface,
and activate phospholipase enzymes, which release arachidonic acid from membrane
phospholipids. Arachidonic acid is converted to cyclic endoperoxides PGG2 and PGH2 by the
enzyme cyclo-oxygenase. These are then converted to thromboxane A2 by thromboxane
synthetase. Thromboxane A2 has a very short half-life and is degraded into thromboxane B2
which is biologically inactive. TxA2 causes shape change and stimulates release reaction from
alpha and dense granules. TxA2 also induces aggregation of other platelets and local
vasoconstriction.
3. Aggregration
This may be defined as binding of platelets to each other. ADP released from platelets or from damaged
cells binds to specific receptors on platelet surface. This causes inhibition of adenyl cyclase and reduction
in the level of cyclic AMP in platelets. A configurational change in the membrane occurs so that receptors
for fibrinogen (GpIIb and IIIa) become exposed on the surface. Binding of fibrinogen molecules to
GPIIb/IIIa receptors on adjacent platelets causes platelet aggregation (Fig. 1.27). The activated platelets
release ADP and TxA2 and so a self-sustaining reaction is generated leading to the formation of a platelet
plug. Thrombin generated from activation of coagulation system is a potent platelet-aggregating agent and
also converts fibrinogen to fibrin. Fibrin and aggregated mass of platelets at the site of injury constitute the
haemostatic plug.

4. Procoagulant activity
 After platelet aggregation and release, the exposed membrane phospholipid (platelet factor 3)
is available for two reactions in the coagulation cascade. Both phospholipid - mediated reactions
are calcium - ion dependent. The first (tenase) involves factors IXa, VIIIa and X in the formation
of factor Xa. Th e second (prothrombinase) results in the formation of thrombin from the
interaction of factors Xa, Va and prothrombin (II). The phospholipid surface forms an ideal
template for the crucial concentration and orientation of these proteins.

(Shirish M Kawthalkar. 2006. Essentials of Hematology. Jaype Brothers Medical Publication)

5. Mention the type of hemofili

Hemofilia adalah gangguan pendarah yang diturukan secara resesif melalui kromosom X, ditandai
dengan terganggunya proses pembekuan darah.
a. Hemofili A: defisiensi atau disfungsi factor pembekuan VII. Sekitar 90% kasus hemophilia
menderita hemofili tipe ini.
b. Hemofili B : defisiensi atau disfungsi factor IX.
c. Hemofili C : Kekurangan factor XI yang diturunkan secara autosomal recessive

(Aru W. Sudoyo, Bambang S, dkk. 2009. Ilmu Penyakit Dalam. Jakarta: Internal Publishing)

6. What are the kind of hemostatis disorders?

1. Von Willebrand Disease
In this disorder disease there is either a reduced level or abnormal function of VWF
resulting form a missense mutation or null mutation. VWF produced in endothelial cells and
megacaryocytes. It has two roles. It promotes platelet adhesion to sub endothelium at high shear
rates and it is the carrier molecule for factor VIII protectic it from premature destruction. The
later property explaining the reduced factor VIII levels found in VWD
2. Diseminated Intravascular Coagulation
Wide spread inappropriate intravascular desposition of fibrin with consumption of
coagulation factors and platelets occurs as a consequence of many disorders release procoagulant
material into the circulation or cause wide spread endothelial damage or platelet aggregation. It
maybe associated with a fulminant haemorrhhagic or thrombotic syndrome with organ
disfunction or un a less severe and more chronic course
3. Vascular bleeding disorder

7. What kind of hemostasis?

a. Haemostasis primer
Terdiri dari trombosit dan pembuluh darah. Disebut hemostasis primer karena yang pertama
terlibat dalam penghentian perdarahan bila terjadi lika atau trauma. Hemostasis primer dimulai
dengan vasokontriksi pembuluh darah dan pembentukan trombosit plak menutup dan
mengenhentikan pendarahan.
 b. Hemostasis sekunder
Terdiri dari factor pembekuan dan anti pembekuan. Hemostasis sekunder dimulai dengan aktivasi
koagulasi melalui jalur ekstrinsik dan intrinsic. Jalur ekstrinsik yaitu jaringan yang terlepas terikat
pada FVII dan menyebabkan FVII menjadi aktif. FVIIa mengaktifkan FX menjadi FXa dan
bersama FV dan PF3 membentuk komplek protrombinase. Selain mengaktifkan FX, FVIIa juga
mengaktifka FIX menjadi FIXa dalam jalur intrinsic
c. Hemostasis tersier
Yaitu system fibrinolysis akan diaktifkan dan menyebabkan lisis dari fibrin dan endotel menjadi
utuh. Pada umumnya proses penyembuhan berlangsung 14 hari.

(Aru W. Sudoyo, Bambang S, dkk. 2009. Ilmu Penyakit Dalam. Jakarta: Internal Publishing)

8. How is the patogenesis of trombosis?

9. How is the phisiology condition of hemostatis?
10. What are the risk factors of hemostatis?
- Pencegahan terjadinya perdarahan
- Pemberian suntikan intramuscular aupun pengambilan darah vena’arteri yang sulit sedapat
mungkin dihindari
- Pemberian obat-obatan yang menganggu fungsi trombosit (asetosal dan OAINS) sebaiknya
dihindari
- Sebelum menjalani prosedur medis invasive harus diberikan factor VII/IX

(Chris Tanto. 2014. Kapita Selekta Kedokteran. Jakarta: Media Aesculapius)

11. Mention the diagnosis of hemostatis and explain it!

12. Explain the management of hemostatis problem!

13. What is the factor of coagulation in hemofily?
14. What is the symptom of hemostatis disorder?
 Gejala hemofili

- Perdarahan oada sendi (hemartrosis) yang tampak sebagai pembengkakan, nyeri atau rasa
kencang pada sendi. Biasanya mengenai sendi lutut, siku dan pergelagan kaki. Biasanya tampak
saat anak mulai merangkak
- Perdarahan di bawah kulit (memar) atau otot atau jaringan lunak yang menyebabkan timbunan
darah pada area tersebut.
- Perdarahan pada mulut dan gusi dan perdarahan yang sulit berhenti setelah menyikat gigi
- Perdarahan berkepanjangan akibat ekstrasi gigi.
- Perdarahan intracranial pada neonates setelah persalinan yang sulit
- Juga dapat terjadi hematuria spontan dan perdarahan saluran cerna, kadang disertai obstruksi
akibat perdarahan intramukosa.

(Chris Tanto. 2014. Kapita Selekta Kedokteran. Jakarta: Media Aesculapius)

15. Apa pemeriksaan untuk menegakkan hemostatis?

1. Blood count and blood film examination
As thrombocytopenia is a common cause of abnormal bleeding, patients with suspected
bleeding disorders should initially have a blood count including platelet count and blood film
examination. In addition to establishing the presence of thrombocytopenia, the cause may be
obvious (e.g. acute leukaemia).
2. Screening tests of blood coagulation
Screening tests provide an assessment of the ‘ extrinsic’ and ‘ intrinsic ’ systems of blood
coagulation and also the central conversion of fi brinogen to fibrin
 The prothrombin time (PT) measures factors VII, X, V, prothrombin and fi brinogen.
Tissue thromboplastin (a brain extract) or t issue factor with lipids and calcium is added
to citrated plasma. Th e normal time for clotting is 10 – 14 s. It may be expressed as the
international normalized ratio (INR) (see p. 375) .
 The activated partial thromboplastin time (APTT) measures factors VIII, IX, XI and XII
in addition to factors X, V, prothrombin and fi brinogen. Three substances –
phospholipid, a surface activator (e.g. kaolin) and calcium – are added to citrated plasma.
The normal time for clotting is approximately 30 – 40 s.
 Prolonged clotting times in the PT and APTT because of factor defi ciency are corrected
by the addition of normal plasma to the test plasma (50 : 50 mix). If there is no correction
or incomplete correction with normal plasma, the presence of an inhibitor of coagulation
is suspected. Th e thrombin (clotting) time (TT) is sensitive to a deficiency of fibrinogen
or inhibition of thrombin. Diluted bovine thrombin is added to citrated plasma at a
concentration giving a clotting time of 14 – 16 s with normal subjects.
3. Specific assays of coagulation factor
 Bleding time
The bleeding time was a useful test for abnormal platelet function including the diagnosis
of VWF deficiency. T e test involved the application of pressure to the upper arm with a
blood pressure cuff , after which small incisions are made in the flexor surface forearm
skin. Bleeding stops normally in 3 – 8 minutes. It has largely been replaced by specific
 platelet aggregation tests, platelet adhesion assays and the platelet function analysis - 100
(PFA - 100) test (see below). Th e bleeding time is prolonged in thrombocytopenia but is
normal in vascular causes of abnormal bleeding.
 Test of thrombosis function
The most valuable investigation is platelet aggregometry which measures the fall in light
absorbance in platelet - rich plasma as platelets aggregate. Initial (primary) aggregation is
caused by an external agent, the secondary response by aggregating agents released from
the platelets themselves. The five external aggregating agents most commonly used are
ADP, collagen, ristocetin, arachidonic acid and adrenaline.
 Test of fibrinolysis
Increased levels of circulating plasminogen activator may be detected by demonstrating
shortened euglobulin clot lysis times. A number of immunological methods are available
to detect fibrinogen or fibrin degradation products (including D - dimers) in serum. In
patients with enhanced fibrinolysis, low levels of circulating plasminogen may be
detected.
(A.V Hoffbrand, P.A.H. Moss. 2013. Essential Hematologi 6th Ed. 2011. UK: Wiley-Blackwell)
16. What is the differencial diagnosis of hemostatis?

(A.V Hoffbrand, P.A.H. Moss. 2013. Essential Hematologi 6th Ed. 2011. UK: Wiley-Blackwell)