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Kasus perdarahan
Pasien datang dengan keluhan bintik-bintik merah
Saran pemeriksaan hemostasis ?
Pasien 1
Kasus perdarahan
Pasien datang dengan keluhan perdarahan dari hidung
Saran pemeriksaan hemostasis ?
Pasien 2
Anamnesis
Klinis
Pemeriksaan hemostasis
Jenis perdarahan
riwayat perdarahan
obat, RPK
jenis perdarahan dll
Perd
ara
han
Bleeding time panjang
Jumlah trombosit normal
PT normal
APTT normal
Perd
ara
han
Bleeding time panjang
Jumlah trombosit rendah
PT normal
APTT normal
Defek kualitatif Defek kuantitatif
THROMBOCYTOPENIA & ETIOLOGY
Thro
mbocy
top
eni
aA. Decrease production
B. Increase destruction
C. Sequestration
D. Dilution
E. Artifactual
• Aplastic
• Infection
• Drugs
• Malignancy (AML, ALL, MDS, solid tumour)
• nutritional
• Toxin: alcohol, cocaine
• Fanconi’s anaemia
• Bernard Soulier Syndrome
• May Hegglin Anomaly
• Wiskott-Aldrich Syndrome
• TAR syndrome
• Rubella
• Autosomal dominant
• B12/folate deficiency
A. Thrombocytopenia: decrease production
Thrombocytopenia:
infection
Thrombocytopenia in viral infections:
• as an almost universal feature of disseminated infection in the neonate or immunosuppressed patient
• as a rare complication of acute transient infection in previously healthy subjects
There are probably two main mechanisms of thrombocytopenia:
• immune mediated platelet destruction with or without immune mediated megakaryocyte damage
• or alternatively direct toxicity to megakaryocytes resulting from viral infection of these cells
Decrease production:
bone marrow supression
Thrombocytopenia:
malignancy
• Replacement normal hematopoetic cells by leukemic cells
Decrease production:
bone marrow supression
• An essential nutrient, vitamin B-12 has a number of
physiological roles including a role in nerve function and cell
growth
• including platelets
• ineffective blood formation in the bone marrow
Thrombocytopenia:
B12/folate deficiencyDecrease production:
Ineffective production
• Immune thrombocytopenia (infections)
• Lupus
• Drugs
• Congenital thrombocyte syndromes
• HIT
• MAHA (TTP, HUS)
• DIC
• HELP
• Eclampsia (?)
• Chronic liver disease
• Collagen vascular d’s
• Primary splenic neoplasm
B. Thrombocytopenia: increase destruction
Thrombocytopenia:
ITPIncrease destruction:
Imune-mediated
There are probably two main mechanisms of
thrombocytopenia in viral infection:
• immune mediated platelet destruction with or without
immune mediated megakaryocyte damage
• or alternatively direct toxicity to megakaryocytes
resulting from viral infection of these cells
Thrombocytopenia:
DICIncrease destruction:
Non-imune-mediated
BT >
Thrombocytopenia
PT >, APTT >
Low fibrinogen
DD >>
• Hypersplenism:
• Infection
• Infammation
• Congestion
• Red cell disorder
• Storage disease
C. Thrombocytopenia: sequestration
Thrombocytopenia:
infectionsIncrease destruction:
sequestration
In bacterial infection thrombocytopenia is usually due
to peripheral causes consumptive coagulopathy and
peripheral sequestration in splenomegaly
D. Thrombocytopenia: dilution
• Massive transfusion
• Replacement of one entire blood volume within 24 h
• Transfusion of >10 units of packed red blood cells (PRBCs) in
24 h
• Transfusion of >20 units of PRBCs in 24 h
• Transfusion of >4 units of PRBCs in 1 h when on-going need is
foreseeable
• Replacement of 50% of total blood volume (TBV) within 3 h.
E. Thrombocytopenia: artifactual
• Platelet clumping & satellitosis Pseudothrombocytopenia
• EDTA-dependent autoantibody:
IgG antibodies formed are directed against the platelet GP
IIb/IIIa complex and the neutrophil FcγRIII
• malignancy, chronic liver disease, infection, pregnancy,
autoimmune diseases, and cardiovascular diseases have
an increased risk of EDTA-dependent
pseudothrombocytopenia
Artifactual thrombocytopenia
(pseudo-thrombocytopenia)
Resolusi:
• Pemeriksaan ulang darah lengkap menggunakan darah sirat (9:1)
• Jumlah trombosit terkoreksi = Hasil trombosit yang didapat x 1,1
Nagrebetsky A et al., Perioperative thrombocytopenia: evidence, evaluation, and emerging therapies, British Journal of Anaesthesia, 122 (1): 19e31 (2019)
Reactive thrombocytosis(secondary thrombocytosis)
• Platelets are acute-phase reactants
• due to the overproduction of pro-inflammatory cytokines IL-1,
IL-6, and IL-11, that occurs in chronic inflammatory, infective, and
malignant states
• Elevated of C-reactive protein (CRP), granulocyte colony-stimulating
factor (G-CSF), and granulocyte-macrophage colony-stimulating
factor (GM-CSF)
• Infection and inflammatory disorders
• Post splenectomy or hypo-splenism
• Malignancy
• Trauma
• Chronic inflammatory conditions
• Hemorrhage, blood loss, or both
• Iron-deficiency anemia
• Rebound thrombocytosis
• Asplenia (anatomic or functional)
• Idiopathic
Reactive thrombocytosis(secondary thrombocytosis)
Reactive thrombocytosis:
iron deficiency anaemia
IDA: expansion of megakaryocyte progenitors an increase
in megakaryocyte ploidy and accelerated megakaryocyte
differentiation
Megakaryocytic cell lines grown in iron-depleted conditions
exhibited reduced proliferation but increased ploidy and cell
size
without changes in TPO
Evstatiev et al., 2014
Thrombocytosis & Malignancy
• clonal thrombocytosis (primary or essential thrombocytosis) is
an unregulated abnormality of platelet production due to a
clonal expansion of bone marrow progenitor cells
• Chronic myeloid leukemia
• Polycythemia vera
• Primary myelofibrosis
• MDS with del (5q)
• MDS/MPN
• POEMS syndrome
• Familial thrombocytosis
Spurious Thrombocytosis
• Microspherocytes
• Cryoglobulinemia
• Neoplastic cell fragments
• Schistocytes
• Bacteria
Spurious thrombocytosis due to thermal injury
• microspherocytosis, spherocytes, fragmentation and blistering
(vesiculation) of RBCs
• extreme heat denaturation of RBC membrane proteins
hemolysis, RBC fragmentation, and vesiculation
• The loss of cell membrane causes the RBCs to lose their
biconcavity and assume the shape of spherocytes and
microspherocytes
• Troubleshooting:
• Peripheral blood smear platelet count
Microspherocytes:
pseudo-thrombocytosis
(Zahid & Alsammak, 2018)
Spurious thrombocytosis due to thermal injury
Widespread red blood cell fragmentation, budding, spherocytes, and
microspherocytes were revealed by microscopic examination (Zahid & Alsammak, 2018)
• Aspirin, thienopyridines and integrin αIIbβ3 antagonists, NSAIDs, antibotics, fish oil
• Renal failure, uremia
• Liver disease
• Anti-platelet antibodies
• Cardiopulmmonary bypass
• MPD, AML, ALL, MDS
• von Willebrand disease type 2B
• Platelet type von Willebrand disease
• Paraproteinemia
Caterina Casari, Wolfgang Bergmeier, Acquired platelet disorders, Thrombosis Research 141S2 (2016) S73–S75
Acquired Disorders of Platelet Function
Konkle 2011
Medications: Aspirin
Acquired Disorders of Platelet Function
Laboratory test:
• Platelet aggregation
Renal failure, uremia
• Bleeding disorder caused by renal dysfunction and azotemia
• Pathogenesis
• abnormal platelet-endothelium interaction
• intrinsic defect of platelets
• dysfunction of GpIIb/IIIa
• defect of adhesion and aggregation
• uremic toxins
• uremic plasma factors that produce NO (endothelium-derived relaxing factor) inhibits platelet aggregation
Addi et al., Tryptophan-Derived Uremic Toxins and Thrombosis in Chronic Kidney Disease Toxins 2018, 10(10), 412;
https://doi.org/10.3390/toxins10100412
Tryptophan-derived uremic toxin (Addi et al., 2018)
tryptophan metabolization in the gut through the indolic and the kynurenine
pathways uremic toxin
von Willebrand disease type 2B
Acquired Disorders of Platelet Function
Ware J., Thrombocytopathy and type 2B von Willebrand disease, The Journal of Clinical Investigation Volume 123 Number 12 December 2013
von Willebrand disease
• is a genetic disorder caused by missing or defective von
Willebrand factor (VWF)
• Role of VWF:
• F. VIII carrier (bind F.VIII)
• Platelet adhesion
• Platelet aggregation
Bernard-Soulier syndrome (BSS)
• autosomal recessive inheritance
• is characterised by missing or functional abnormal platelet GPIb/V/IX complexes
• absent or markedly reduced adhesion and agglutination/aggregation inresponse to ristocetin or low concentrations of thrombin
• characterized by a prolonged bleeding time, large platelets and thrombocytopenia (varied)
Glanzmann thrombasthenia
• Disorders of platelet
aggregation
• autosomal recessive
disorder
• is caused by an abnormality
in the genes for
glycoproteins IIb/IIIa
• Deficiency of Gp IIB/IIIa
Von Willebrand
disease
Glanzman
thrombasteniaBernard Soulier
syndrome
• Easy bruising
• Nose bleeds
• Bleeding gums
• Heavy menstrual periods
• Gastrointestinal bleding
GIT bleeding
Von Willebrand
disease
Glanzman
thrombastenia
Bernard Soulier
syndrome
Diagnosis of Inherited Platelet function
disorders
• Platelet count normal
• BT >
• Closure time >
• PT & APTT normal
• LTA: RIPA decreased
• vWF Ag: decreased
• Platelet aggregation (ADP): normal
• APTT > type 2N
• F. VIII < type 2N
• Platelet count normal
• BT >
• closure time >
• PT & APTT normal
• LTA: platelet aggregation fails to occur with any agonist, except ristocetin
• GpIIb/IIIa not detectable (flowcytometry)
• Platelet count normal/decrease
• BT >
• Closure time >
• PT & APTT normal
• LTA: RIPA decreased
• Platelet aggregation (ADP): normal
• Giant platelets
Von Willebrand
diseaseGlanzman
thrombastenia
Bernard Soulier
syndrome
Platelet aggregation of inherited platelet
function disorders
Algorithm for management of thrombocytopenia
Erkurt et al., Thrombocytopenia in Adults: Review Article, J Hematol • 2012;1(2-3):44-53
Pemeriksaan laboratorium hemostasis
Jenis perdarahan
Riwayat perdarahan
Skrining hemostasis
Bleeding time (BT)
Clotting time (CT) tidak direkomendasi !
PT
APTT
Fibrinogen
D-dime
Pemeriksaan khusus
Kesimpulan
Penyakit perdarahan terkait abnormalitas trombosit
diwaspadai pasien dengan perdarahan mukokutaneus
Platelet disorders kualitatif & kuantitatif, didapat &
herediter, imun & non imun
Perlu dilakukan pemeriksaan skrining hemostasis BT
memanjang, jumlah trombosit N/rendah/tinggi, dengan
PT dan APTT N/panjang
Perlu pemeriksaan lanjutan