Plenary 3 - Gangguan Hemostasis dan Trombosis

PLENARY 328D

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Esha Almara 1110312155 Rurin Ardiyanti 1110311024 Nadiah Ismail 1110312018 Anelia Tiara Suci 1110313098 Cindy Aulia 1110313059 Dani Putra Amerta 1110312035 Esha Almara 1110312155 Putri Maghfirah Bahri 1110312065 Rizky Dwi Utami 1110313067 Satrya Aji Pamungkas 1110312051

INCESSANT BLEEDINGMufi, boy aged 10 years, was brought to the clinic

because of his bleeding not being stopped after circumcision done by the head nurse in the village. From anamnesis Mufi often have swelling in the knee since childhood. On examination, seen blood seeps in kassa that covering the wound Circumcision. The results of laboratory tests of blood routine normal, checking filter hemostasis obtained 270.000/mm3 platelet count, bleeding time 1'30'', clotting time 15 '. Mufi immediately referred to hospital with suspected hemorhagik diathesis.

In M.Djamil Mufi undergo further examination and obtained hematologic within normal limits, PT 11’’ and APTT 60’’. Mufi then planned for factor assay examination, while for initial management done cryoprecipitat transfusion.

In the hospital, Mufi met a mother 60-year-old with right leg swelling and pain. according to the mother, she had blockage of blood vessels in the legs.

How do you explain what happened to Mufi and mother as well as the therapy?

TERMINOLOGY

1. hemorrhagic diathesisBleeding tendency in the hemostasis system

2. Bleeding timeTests to measure the time required for the cessation of blood flow, dimuali of blood discharge from the network. The purpose of this inspection is to evaluate the function of blood vessels and hemostasis systems

3. Clothing timeTime used the blood to clot. The function of this inspection was to assess the clotting factor

4. CryopresipitatDeposition of substances in solution after cooling as factors in blood plasma hemofilik

...TERMINOLOGY

5. PT (protombin time)Protombin conversion speed to thrombin in a given area and additional calcium citrate. Its function is to assess the extrinsic coagulation pathway and common pathway

6. APTT (activated partial thromboplastin time)Examination of coagulation factors to assess the intrinsic coagulation time on track

7. factor assayExamination to test the activity of clotting factors, and performed an elongated PT or APTT

Define Problem

1. Why mufi’s bleeding didn’t stop?2. Why mufi often swollen knees as a child?3. How did the clinical interpretation of laboratory

tests?4. Is there any effect of age and sex mufi against

illness?5. What is the basis of a doctor's diagnosis of

hemorrhagic diathesis disease?6. What is the interpretation of further

investigation?7. Why mufi are advised to check the assay factor?8. Why do cryoprecipitate administration before

making any factor screening assay?

…Define Problem

9. How is the relationship with a swollen knee mufi bleeding after circumcision?

10. What causes blood vessel blockage mother?11. Is there a connection between swelling and

pain experienced by the mother?12. Is the same mufi experienced swelling with

mothers who met?13. Is the age of the mother is a trigger swelling

and pain they experienced?14. What should be given to treatment of the

mother and mufi?15. Is there a procedure of beginning, except

cryopresipitat?16. Why swelling only occurs on the right leg?

Analysis problem1. The cause of the bleeding does not stop:

There might be abnormalities in hemostasis system- Platelets unable to aggregate- clotting factor disease hemophilia- Blood vessels brittle

2. Mufi frequent cause of knee swelling:- Damage caused by bleeding synovial joints each friction- The knee is a hinge joint, so it is not resistant to a twisting motion absolute blood vessel damage

3. Interpretation of clinical laboratory tests:- Platelets 270.000/mm3 normal (150,000 - 400.000mm3)- BT 1.5 minutes (1-6 minutes)- CT 15 minutes when using the tube is still considered normal (9-15 minutes), but an object is said elongated glass clotting factor disorders

...Analysis problem4. Effect of age of 10 years old:

If mufi mufi including hemophilia mild hemophilia, because the onset> 2 yearsInfluence of sex:If mufi hemophilia men more often show clinical manifestations

5. Primary diagnosis of hemorrhagic diathesis:- The blood that do not stop after circumcision- Based on laboratory tests with CT elongated

6. Interpretation of further investigation:- PT 11 seconds normal (11-15 seconds)- APTT 60 seconds elongated (20-40 seconds)There may be a disorder intrinsic pathway

...Analysis problem7. Basic checks assay factors:

- APTT increased- If mufi hemophilia, to determine the type of hemophilia

- To determine what factors deficiency

8. Causes of cryoprecipitate given first:- There are factor VIII, when mufi disease hemophilia A- That do not stop bleeding- the cause is unknown. So, cryoprecipitate also treat diseases

hemoagik diathesis such as von Willebrand disease, hipofibrinogenemia, and other coagulation factor deficiencies.

- Cryoprecipitate an initial relief in patients hemorrhagic diathesis

9. Relationships with bleeding knee swelling post:- circumcisionBoth of these symptoms are signs of hemostasis disorders

...Analysis problem10. Causes of deep vein thrombosis:

- Hypertension turbulence platelet vascular endothelial contact with ill

- High cholesterol thrombosis allow clog blood vascular- Hiperfungsi platelets- Immobilization static blood flow blockages

11. Swollen and painful relationship:Vascular endothelium is able to issue protalgladin capable of destroying thrombus. Meanwhile prostalgladin able to stimulate nerve pain

12. Yes, mufi and mother equally impaired hemostasis system

13. Yes, because:- At the age of 46-72 years old, the incidence of thrombosis by 62%- Old age is susceptible to autoimmune arthritis can cause

reumathoid- Old age are particularly vulnerable occurrence of thrombosis

...Analysis problem14. Treatment of disease mufi:

- Determine a definite diagnosis first. Then do the proper management of- Conducting joint care- Provide education about trauma- Advise malakukan routine examination of clotting factors- Do not give aspirinManagement of maternal disease:- Causal therapy- Give anticoagulation

15. Another early Procedures:Give oral desmopressin factor VII

16. Causes swelling of the legs just right:Effect of activity right leg more often a pedestal

Schema

Learning Objectives

Students are able toexplain: Definition Etiology Classification Risk factors Epidemiology Pathogenesis Clinical symptoms Laboratory

abnormalities Basic diagnostics Therapy Complication Referral cases

Of:

1. Diathesis Hemorragic

2. Trombosis

HEMOSTASIS

HEMOSTASIS

Maintain the blood solution & cover endotel from damage. Consist of : Vaskular,Trombosit,Coagulation,Fibrinolisis

If this system: Balanced Normal hemostasis Lacking Bleeding (dithesis

hemorragic) Overload thrombosis

DIATHESIS HEMORRAGIC


Vascular disorders Acquired : Purpura Herediter : Talangiectasia herediter

hemorragic Trombosit disorders

Trombopati Trombositopenia : PTI

Coagulation factor disorders Acquired : Vit.K deficiency, DIC Herediter : Hemofilia, vWD






PURPURA TROMBOSITOPENIK IDIOPATIK / PTI

PURPURA TROMBOSITOPENIK IDIOPATIK

Definition : Abnormalities due to thrombocytopenia

Etiology : - idiophatic

- autoimun

Klasifikasi :PIT acute

Often in children, after an acute viral infection / vaccine. Most of the recovered spontaneously, 5-10% become chronic

PIT kronicOften in women 15-50 years old. Chronic, recurrent. Rarely cured spotan.Sumber:ipd,hematologi klinik ringkas, hematologi-

onkologi anak

Patogenesis :

Trombosit-Ab (IgG) antibody coated platelets difagosit

makrofag dlm RES trtma lien trombositopenia

kompensasi SST megakariosit utk mmbntk trombosit.

Clinical Manifestation:- Onset slowly by bleeding through the skin /

mucosal form: petechie, echymosis, easy bruising, mwnorrhagia, epistaxis, or bleeding gums.

- CNS bleeding rarely, if occurred fatal- Splenomegaly <10%

Lab abnormalities:1. peripheral blood: Trombosit 10-50rb/mm³2. SST : megakariosit3. Immunology: The anti-platelet IgG on the

surface of platelets / within serum (gpIIb / IIIA or GPIB).

Diagnose: ITP enforced if 4. skin or mucosal bleeding5. thrombocytopenia6. SST: normal or increased megakaryocytes7. Antiplatelet antibodies (IgG) positive8. No cause of secondary thrombocytopenia

Therapy

1. Therapy to reduce the immunea. Corticosteroids (prednisone 60-80 mg / day and lower dose slowly about 15 mg / hr)

- Suppression of macrophage activity that decreases platelet

destruction- << Binding of IgG and suppress antibody

synthesisb. Within 3 months not responding:

- Splenoktomi-most brespon good- Other immunosuppressant drugs (vincristine,

azathioprim)2. Supportive therapy to reduce the influence of

thrombocytopeniaa. Androgens (danazol)b. High dose Ig to suppress the function of macrophagesc. Platelet concentrates transfusion if the patient is at risk of bleeding

Complication Hemorrhages Impairment of

consciousness Splenomegaly

Referral : (2) Prognosis: In generally good. In

children sometimes happen complete remission without treatment.

10% become chronic ITP and <1% died.

± 90% of patients with ITP in remission after receiving treatment for 3 weeks, 3 months and no more symptoms arise.

In adults often relapse within 4-15 years.

Worse prognosis in pregnant women and if there are complications, especially bleeding of the brain that can lead to death.






Hemophilia

HEMOFILIA A & B

Definition : Hereditary disorders, blood coagulation function difficult to clot.

Etiology : A - factor VIII deficiencyB - Deficiency of factor IX• Hereditary or

spontaneous mutations in> 30% of cases.

Classification:1. Severe hemophilia: clotting factor

<1%2. Moderate hemophilia: 1-5%

clotting factor3. Mild hemophilia: 5-30% clotting

factor

Sumber:ipd,hematologi klinik ringkas, hematologi-onkologi anak

Epidemiology:• The most frequently encountered• The incidence of 1-2 per 10,000 population / year• Hemophilia A 85%• Hemophilia B is 15%• Manifest in men, in women carrier• Hereditary (X-linked recessive / Xh) or spontaneous

mutation> 30% of cases

Patogenesis :• Hemofilia A – def F.VIII clotting activity krn penurunan sintesis

atau pembentukan F.VIIIC dg struktur abnormalDef F.VIII Jal. Intrinsik terganggu pmbentukan fibrin berkurang.

• Hemofilia B – def. F.IX

Clinical Manifestation:- Bleeding from childhood: when circum, tooth extraction, or

injury posttrauma- Frequent spontaneous bleeding, especially bleeding joints

(haemarthros) at the hinge joint. Haemarthros repetitive joint damage (anklylose) and impaired walking. Bleeding muscles (especially the flexor muscles such as the calf muscles, hip and forearm), hematoma, oral mucosal bleeding, intracranial (peny.kematian), epistaxis and hematuria.

Lab abnormalities:1. Hemostasis Filter test

-Elongated APTT (normal in mild hemofili)-BT, PT, TT normal

2. Confirmatory tests- Quantitative measurements F.VIII & F.IX- If F.VIII << proceed with the examination of vWF

3. Examination of karrier women - F.VIIIC also decreased (50%)

DD/:Hemofilia A Hemofilia B vWD

Inhiritance Sex linked Sex linked Autosomal dominan

Tempat perdarahan Otot, sendi, posttrauma

Otot, sendi, posttrauma

Mukosa, luka kulit, posttrauma/operasi

BT N N Memanjang

PT N N N

APTT Memanjang Memanjang Memanjang

F.VIIIC Rendah N N

F.VIIIR:AG (vWF) N N Rendah

F.IX N Rendah N

Tes Ristosetin N N (-)

1. Providing F.VIII – Hemofilia A & F.IX – hemofilia B lifetime-Cryoprecipitate (F.VIII, vWF, fibrinogen, F.XIII)-Lyophilized F.VIII - Lyophilized F.IX-prothrombin complex concentrate (vit.K – dependant factor)

3. Gen therapy(?)4. Mild hemophilia : DDAVP. 5. Overcome acute hemorrhage with Rest,Ice,Compressio,Elevation

Preventive therapy:Health education to prevent disability-Keep your ideal body weight. Obesity is a higher risk of joint bleeding-Avoid injuries and impact-Maintenance teeth and gums- Vitamin K-Avoid giving aspirin, salicylic acids, AINS, heparin

Rehabilitative therapy: Artritis hemophilia – exercise passive / active, hot and cold therapy, the use of orthosis, psychosocial therapy, recreational therapy and education

Curative therapy:

Complication :-Progressive arthropathy-Hepatitis (transfusion)-Allergic reactions – due to transfusion of blood products-Antibody formed as an antagonist to f.VIII & IX-Hemolytic anemia-AIDS (HIV) due to exposure to contaminated blood products..

Referral: (2)

Prognosis: Indeed, there is no word 'cured' for hemophilia. Without treatment most children died of severe hemophilia, but with the right treatment to ensure children grow up normal and productive adulthood. Availability of fresh blood facilities, kropresipitat and F VIII causes hemophilia a good prognosis.






VON WILLEBRAND DISEASE

VON WILLEBRAND DISEASEDefinition : Reduced synthesis of vWF resulting in:- Impaired platelet adhesion- Decrease in activity within the plasma F.VIIIC

Classification :• Tipe 1 – decreased synthesis of vWF• Tipe 2 A - Impaired synthesis of large & moderate vWF

multimers B – formation of large vWF multimers

abnormal so quickly removed from the blood.

• Tipe 3 – vWF synthesis nonexistent

Epidemiology :• Type 1, the most common of about 70-80%.• Type 2, there are subtypes 2A, 2B, 2N, and 2M)• Type 3, the most severe / serious clinical manifestations.• Are common in the West, in the INDO not many.• Inherited autosomal dominant

Patogenesys :<< vWF vWF can not act as adhesive to hold the platelets

in the blood vessels around the area were damaged. Platelets can not coated blood vessel walls.

<< vwF vWF reduced activity of factor VIII vWF carrying factor VIII. Factor VIII is needed to form a strong

network. In the absence of factor VIII in the normal amount of the blood clotting process will take longer.

Clinical Manifestation:• Abnormal bleeding (epistaxis, menorrhagia, bleeding

from cuts, tooth extraction or postoperative, major bleeding, hematoma, bleeding rarely joints

• Easy bruising

Lab abnormalities:1. BT ectends2. APT slightly 3. Ristocetin induced platelet aggregation test (-), except

type IIb4. Elektroforesis : vWF decrease in type I or 0 in type III5. Imunoelektroforesis : big multimers (-) in tipe IIa

big multimers (-) moderatemultimers in type IIb

DD/ :Should be distinguished from hemophilia, in vWD:• BT extends• Ristocetin test (-)• VWF levels decreased

Therapy :1. Infus Desmopressin (DDAVP) 2. Cryoprecipitate3. Epsilon aminocaproic acid / asam traneksamat (inhibitor

fibrinolitik)

Komplikasi :• Anemia.• Deaths due to bleeding.• Antibodies to vWF and F.VIII in type III patients

Referral: 1






Vit. K deficiency

Vitamin K Deficiency Bleeding (VKDB)

Definition : Tendency to bleed due to coagulation disorders because lacking of vitamin K

Etiology :1. Less input1. Disrupted absorption2. Inhibitory function of

Vit.K by antikoagulan, antikonvulsan, anti TBC

3. Long term Antibiotik

Classification :1. Early VKDB2. Classical VKDB 3. Late VKDB


Epidemiology:• The incidence ranged from

1:200 to VKDB 1:400 births who did not receive of vitamin K prophylaxis. In Indonesia, data on national VKDB yet available. Through 2004 found 21 cases in RSCM Jakarta, 6 cases at the hospital Dr. Sardjito Yogyakarta and 8 cases in RSU Dr. Soetomo.

Risk factors:• mother during pregnancy

taking medications that interfere with of vitamin K metabolism

• synthesis of of vitamin K by intestinal bacteria less (use of antibiotics, especially in preterm infants)

• impaired function of the liver (cholestasis)

• lack of of vitamin K intake can occur in infants who are breastfed exclusively morbidly

• Malabsorption syndrome and chronic diarrhea.

Patogenesys :• Vitamin K is necessary for the synthesis of procoagulant

factors II, VII, IX and X (prothrombin complex) as well as the anticoagulant proteins C and S

• In the liver, prothrombin complex is stored in an inactive form, Vitamin K is required to activate it

Clinical Manifestation :

• Bleeding, especially in the umbilicus, mucous membranes, gastrointestinal tract, circumcision and venous puncture. Can be a hematoma at the site of trauma, such as hematoma sefal. Result is the emergence of further intracranial hemorrhage is a cause of mortality or morbidity were settled. Bleeding is often a skin purpura, ecchymoses or bleeding through needle puncture marks.

• pale• mild hepatomegaly

Lab abnormalities:1. PPT elongated2. APTT normal3. TT normal

Diagnose : Established if there is clinical suspicion, perform laboratory tests.

Therapy: If there is major bleeding give 25mg subcutaneous VitK1. Also give transfusion of fresh plasma or fresh frozen plasma. Prophylaxis: VitK 5mg/day peroral

Complication : Intracranial hemorrhage in newborns

Prognosa: If treated the prognosis is very good. Symptoms usually disappear after giving vit.K or later than 24 hours thereafter.

Referral case: thoroughly handled(4)






Disseminata Intravascular Coagulation (DIC)

KOAGULASI INTRVASKULAR DISEMINATA(DIC)

Definisi : Clinical syndrome because deposition (deposition) systemic fibrin and in the same time there bleeding tendency.

Characteristics:Uncontrolled activation of coagulation and fibrinolysis. Can occur in acute, chronic and subacute


• Epidemiology :

DIC can occur in 30% -50% of patients with sepsis. In addition it is estimated DIC occurs 1% of all patients admitted to the hospital. In the United States approximately 18,000 cases occur DIC in 1994.

Etiology:

• Infection (dengue hemorrhagic fever, sepsis, meningitis, pneumonia, malaria, tropical, infection by some types of rickets).

• Complications of pregnancy (solutio placenta, intrauterine fetal death, amniotic fluid embolism).

• After surgery (lung surgery, by pass cardiopulmonal, lobectomy, gastrectomy, splenectomy).

• Malignancies (prostate carcinoma, lung carcinoma, acute leukemia).

• Transfusion reactions, shock anafilatik, extensive tissue damage (burns / trauma), severe liver damage / gigita

Patogenesis

Clinical symptoms:• Bleeding: skin(petechie and echymosis), mucosal

(epistaxis, bleeding gums, hematemesis, etc.), easy bruising and bleeding organs

• Hemorrhagic tissue necrosis and occlusion of multiple small blood vessels leading to multiorgan failure:a. renal failureb. Gangrene in peripheralc. Jaundice - liverd. Decreased consciousness - the brain

• Basic disease symptoms

Lab Abnormalitis:1. Pheripheral blood & trombosit count : Trombositopenia2. APTT, PT & TT elongated3. Fibrinogen plasma decrease4. FDP (fibrinogen degradation product) increase5. F.VIII & F.V decrease6. Pheripheral blood: anemia mikroangiopatik7. DD-dimer (+)8. Tes parakoagulasi (+)

Diagnose: Diagnosis is based on clinical symptoms and laboratory results. Minimal criteria for DIC diagnosis are manifestations of bleeding, thromboembolism or both accompanied tromboitopenia and burr cell picture in RBC or DD-dimer (+)

Therapy :1. Basic disease therapy2. Supportive therapy with fresh blood, fresh frozen

plasma, or platelet concentrate fibrinoge (When the fresh blood platelet counts remained low up to a week)

3. Giving heparin 200 U / kg iv every 4-6 hours. The increase in plasma fibrinogen levels evident in 6-8 hours, after 24-48 hours after reaching normal values .

Complication : (because multiorgan failure)- Acute respiratory distress syndrome (ARDS)- Decreased kidney function- CNS Disorders- Impaired liver- Gastrointestinal mucosal ulceration: bleeding- Increased cardiac enzymes: ischemia, arrhythmias- Purpura fulminant- Adrenal Insufficiency- More than 50% death

Prognosis: Depending in etiology and treatment of the primary disease and coagulopathy.

Rujukan : (2) for the treatment refer to a specialist






PLATELET FUNCTION DISORDERS/ Trombopati

TROMBOPATIClassification : 1. Hereditary disorders

- Disease Glanzmann - Platelet Aggregation disorder- Bernard-Soulier syndrome - disorder platelet adhesion- Storage Disease - platelet secretion disorder

2. Acquired disorders- Anti-platelet drugs: inhibitors of the enzyme cyclooxygenase- Hiperglobulinemia: disruption of adhesion and the enzyme cyclooxygenase- Abnormalities mieloproliperatif & mielodisplastik- Uremia- Heart Disorders: less all coagulation factors and impaired adhesiontherapy: DDAVP / cryoprecipitate / platelet transfusions

Clinical Symptomp:• Variable, bruising until bleeding• Often found in the form of petechie, skin

bruising, mucosal bleeding nose, vagina and bleeding that elongated to the wound.

Lab Examination:• Platelet count - normal / slightly decrease• BT - elongated• Test PT, APTT - normal• Test fibrinolysis - normal

Syndrom Bernard-Soulier

• Autosomal resesif• GPIb not found in the membranes of platelets• GK: bruising / bleeding• P.Lab:-Trombosit N/slightly <<

-BT elongated - clot retraction N -SADT: giant platelet

• Terapi: Transfusi eritrosit dan trombosit

Glanzmann Disease

• Autosomal resesif• Rare • << GPIIb/IIIa• GK: The bleeding is not too severe (ptekie,

perdarahan mukosa, epistaksis, menorrhagi, perd GI)• P.Lab :- jumlah & morf trombosit N

- BT elongated- Clot retraction did not occur

• Terapi: Transfusi trombosit

Storage Pool Disease

• Dense granul <</(-)• BT elongated• Pheripheral trombosit morfology normal• Clinical manifestation: Mild – severe bleeding

TROMBOSIS

TROMBOSIS

Definition: Obstruction of bloodflow formed of trombosit & fibrin.

Etiology : Blood flow

deceleration Blood

hypercoagulability

Endotel damage

Classification : Arteri Trombosis Vein Trombosis

Sign & Symptom : Pain swollen Numb

Complication : Emboli

Arterial Trombosis

White trombus (>> trombosit & fibrin) Inflamation sign more severe than

vein trombosis Risk factor :

Man Hyperlipidemia DM Smoke F.VII & Fibrinogen increase Hypertensi

Vein Trombosis

Red trombosis Usually beian from calf vein and

extends to vena proksimal Risk Factor:

Statis/Immobilization Idiopathic Herediter (mutasi F.V Leiden, Antitrombin

deficiency, Protein C deficiency, Mutasi G20210A, Defek fibrinogen)

Acquired (post-operation, malignancy, antifosfolipid syndrom)

Vein Trombosis

Diagnose : Venografi (gold standar) USG doppler MRI D-dimer

Trombosis Examination

Blood count & LED Peripheral blood smear PT, APTT TT Fibrinogen examination protein C resistance test DNA test – F.V Antitrombin Protein C & Protein S

Therapy

PHARMACOLOGY

Anti Coagulan Heparin Anticoagulan oral

Anti platelet aggregtion Aspirin, klopidrogel,

Tiklopidin, Dipisidamol

Trombolitik / Fibrinolitik Streptokinase,

Urokinase, rTPA

NON-PHARMACOLOGY

elevate the extremities position

warm compresses the scope of the

joint exercise elastic stockings

Documents

Plenary 3 - Gangguan Hemostasis dan Trombosis