Thrombocytopenia and Thrombocytosis

Mediarty Syahrir Hemato-Oncology Medic Division Of Internal Medicine Department Sriwijaya Universitiy/Dr.M.Husein General Hospital Palembang Blok 14 September 2012

Thrombocytopoiesis
PLURIPOTENT MIXED STEM CELL PROGENITOR CELL COMMITTED PROGENITOR CELL RECOGNIZABLE BONE MARROW PRECURSOR CELL pronormoblast myeloblast monoblast MATURE BLOOD CELL red cell neutrophil monocyte eosinophil basophil megakaryocyte lymphoblast lymphoblast platelet T-cell B-cell
& plasma cell

BFU-E/CFU-E CFU-GM CFU-Eos myeloid progenitor cell pluripotent stem cell lymphoid CFU-Baso CFU-Meg pre-T pre-B

Platelets in the circulation: Influx, efflux, and redistribution

(+) Thrombopoietin
platelet count

PRODUCTION

CIRCULATING PLATELETS
70%

DESTRUCTION or REMOVAL

SPLEEN
30%

Thrombopoietin
normal platelet count
plasma TPO platelet

thrombocytopenia

[TPO] total

normal

normal
increased

[TPO] free

normal

Thrombocytopenic bleeding

Risk of bleeding
Platelet count Cause of thrombocytopenia Comorbid disease Drugs

Clinical manifestations Ptechiae Purpura, Echymoses Mucosal bleeding Menorrhagia Intracranial bleeding

Approach to thrombocytopenia
THROMBOCYTOPENIA rule out pseudothrombocytopenia SEQUESTRATION
look for splenomegaly
Causes of splenomegaly infection inflammation congestion malignancy red cell disorders storage diseases

PRODUCTION
bone marrow investigation review meds

DESTRUCTION
look for underlying disorders review meds

aplasia immune infiltration auto-immune (ITP, SLE ineffective megakaryopoiesis drugs eg. MDS infections selective impairment of platelet allo-immune production non-immune sepsis DIC, TTP, HUS hypertensive disorders of pregnancy

Thrombocytopenia: Differential Diagnosis

Pseudothrombocytopenia Dilutional Thrombocytopenia Decreased Platelet production Increased Platelet Destruction Altered Distribution of Platelets

Pseudothrombocytopenia

Tidak ditemukan ptekiae dan ekimosis Sering disebabkan oleh platelet clumping
Anti koagulan : EDTA Berhubungan dg adanya autoantibodies

Dilusional Trombositopenia

Transfusi masiv pd terapi perdarahan

Penurunan Produksi trombosit

Fanconis anemia Paroxysmal Nocturnal Hemoglobinuria Viral infections: rubella, CMV, EBV,HIV Nutritional Deficiencies: B12, Folate, Fe Aplastic Anemia Drugs: thiazides, estrogen, chemotherapy Toxins: alcohol, cocaine

Causes of Thrombocytopenia
Decreased production of platelets Bone marrow failure syndromes Congenital (amegakaryocytic thrombocytopenia, Fanconis anemia, dyskeratosis congenita, Schwachmann-Diamond syndrome, thrombocytopenia-absent radii syndrome, WiskottAldrich Syndrome) Acquired (aplastic anemia, amegakaryocytic thrombocytopenia) Myelodysplasia Marrow infiltration (neoplastic, infectious) Chemotherapy-induced Irradiation-induced Folate, B12, or iron (advanced cases) deficiency Alcoholism

Peningkatan Destruksi trombosit

Penyebab terbanyak Merangsang terjadinya trombopoisis dg meningkatanya jml, ukuran dan kecepatan pematangan megakaryosit. Meningkatkan konsumsi trombus intravaskular atau kerusakan permukaan endotel.

Peningkatan Destruksi (lanj..)

ITP HIV associated ITP Drugs: heparin, gold, quinidine,lasix, cephalosporins, pcn, H2 blockers DIC TTP

Merubah Distribusi Trombosit

Trombosit di sirkulasi menurun, tetapi jumlah trombosit masih normal Hypersplenism

Leukemia Lymphoma

Profilaksis Versus Terapeutik Transfusion Trombosit

Platelet transfusions for active bleeding much more common on surgical and cardiology services Prophylactic transfusions most common on hem/onc services 10 x 109/L has become the standard clinical practice on hem/onc services

ITP- Immune/Idiopathic Thrombocytopenic Purpura

Definition : Isolated thrombocytopenia with no clinically appearent associated conditions or other causes of thrombocytopenia Etiology : antibodies directed against platelets coat platelets surface, Ig-G coated platelets are taken up by RE system Incidence : approximately 100 permillion; half of these are children. In adults, two peaks: - one are young (<40 ), with female predominance, - one are older (>60), no gender predominance

Clinical forms

Acute in children (2 to 4 years) Follows infection Chronic in adults (20 to 50 years) No specific cause

Risk factors

Diseases SLE, HIV / AIDS Drugs Sulfonamides, Ibuprofen, Ranitidine, Phenytoin, Tamoxifen

ITP: Laboratory features

ITP IS A DIAGNOSIS OF EXCLUSION no sensitive and specific test for ITP isolated thrombocytopenia normal PT, PTT bone marrow investigation not essential in straightforward cases

Adult ITP - laboratory investigations

Repeat FBC Examine blood film

Pseudothrombocytopenia (0.1% adults, use citrate) CLL, MDS, megaloblastic anaemia, MAHA

Autoimmune screen

Lupus and other autoimmune diseases

Coagulation screen - not recommended

Bone marrow?

Adult ITP - antiplatelet antibodies

PAIg in most patients with ITP (Direct PIFT)

BUT PAIg often in non-immune thrombocytopenias

Antibodies to specific glycoproteins (GP) IIb/IIIa (MAIPA)

Even less sensitive (50-65%) But more specific (90%) in ITP

Adult ITP - Helicobacter pylori

Implicated in gastritis, peptic ulcers, autoimmune disease Italian study 30 refractory ITP patients H pylori (+) in 30% cases Rx with triple therapy Improvement in platelet count in 92%
CR in 33% PR in 16%

Breath test or blood test Worth checking if refractory

Emilia et al, Blood 97, 812 (2001)

ITP: Treatment Patient is not bleeding

plt > 50: Rx not indicated plt 20-50: Rx usually not needed, monitor closely plt < 20: Rx indicated with one or more of:
prednisone IVIG anti-D if Rh pos splenectomy if relapsing severe ITP

(No role for prophylactic platelet transfusion)

ITP: Treatment Patient is bleeding

For serious bleeding (eg. CNS, retroperitoneal, GI)

Prednisone and IVIG Transfuse platelets consider urgent splenectomy Provide other supportive/resuscitative care as needed

Adults: second line therapy - splenectomy

2/3 will respond Need platelets >30 x 109/L for splenectomy Vaccination Pneumovax, Hib, Meningococcal C 2 weeks pre-op Other prophylaxis Penicillin 250-500mg bd (or equivalent) ?for life ?2 years Annual flu vaccine + Pneumovax booster 5 yearly Can we predict response?

ITP: therapy in adults

First line Prednisolone IVIg Second line Observe Dexamethasone Methylprednisolone High dose IVIg Anti-D Dapsone Azathioprine Cyclosporin Cyclophosphamide Combination chemoRx Vinca alkaloids Fail 1st & 2nd Observe Intermittent IVIg/steroids Combination chemoRx

Experimental Mycophenolate Rituximab Campath

Splenectomy

Pregnancy: management of ITP

Asymptomatic women,platelets >20 x 109/L

Do not need treatment until delivery is imminent

Safe for normal vaginal delivery Safe for caesarean section, spinal or epidural anaesthesia

Platelet counts >50 x 109/L

Platelet counts >80 x 109/L

POLISITEMIA VERA

Polisitemia vera

kelainan klonal pd sel progenitor hemopoetik multipoten dmn tjd akumulasi eritrosit, granulosit, & platelet dg fenotip normal, tanpa dijumpai adanya rangsangan fisiologik. Insiden 2,3 per 100.000 populasi pertahun Usia 40-60 th Rasio laki-laki & wanita 2:1 Survival median 1,5 3 tahun, dengan pengobatan bisa >10 tahun

Tanda dan gejala

Gejala awal: Sakit kepala, telinga berdenging, mudah lelah, gangguan daya ingat, sulit bernafas, darah tinggi, gangguan penglihatan, rasa panas pada tangan & kaki, gatal, perdarahan hidung, lambung, atau sakit tulang. Gejala akhir: Perdarahan atau trombosis Peningkatan asam urat gout & resiko ulkus peptikum Fase splenomegali: Gagal ss tulang anemia berat, hepatosplenomegali

Erythromelalgia

Patofisiologi

Hiperviskositas kecepatan aliran eritrostasis laju transport O2 oksigenasi jaringan terganggu timbul gejala (iskemik/infark) Penurunan kecepatan aliran. Ggn fungsi hemostasis primer trombosis perdarahan. Trombositosis Basofilia (basofil > 65/ml). Histamin gatal, gastritis dan perdarahan. Hepatomegali, splenomegali, akibat hiperaktif hemopoesis ekstrameduler Laju siklus sel yang tinggi, produksi as urat Defisiensi asam folat & B12 kelainan kulit & mukosa, neuropati, atrofi N. optikus, psikosis

Genetics

JAK2 V617F mutation is associated with all CMPDs (except CML)

Present in up to 97% of PV patients Janus kinase/signal trasducers and activators of trascription (JAK/STAT) pathway plays a central role in initiating signal transduction from hematopoietic growth factor receptors V617F mutation releases the autoinhibitory action of the JAK2 domain and results in increased expression Even in the absence of growth factor, JAK2 V617F continues to signal transcription of hematopoietic precursors.

Laboratorium

Eritrosit pria >6 jt/mL, wanita >5,5 jt/mL Preparat hapus: normokrom normositik Granulosit 12-25 rb/mL. 1/3 kasus: basofilia Trombosit 450-800 rb/mL. kadang >1jt. Morfologi abnormal. B12 serum dapat meningkat (35%), atau menurun (30%) BMP tidak diperlukan utk diagnostik. Hiperplasia trilinier: seri eritrosit, megakariosit & mielosit. Histopatologi ss tulang khas: morfologi megakariosit yg abnormal & sedikit fibrosis Sitogenetika: ditemukan kariotipik

Bone Marrow Biopsy

Hypercellular with increased megakaryocytes, giant megakaryocytes, and decreased marrow iron stores

Diagnosis

Penatalaksanaan

Menurunkan viskositas & mengontrol eritropoesis dg flebotomi Menghindari pembedahan elektif pd fase eritrositik/polisitemia yg belum terkontrol Menghindari over treatment Mengontrol panmielosis dg fosfor radioaktif atau sitostatika pd pasien diatas 40 th, terutama bila disertai: trombosis dg atau tanpa perdarahan leukositosis progresif splenomegali simtomatik atau menimbulkan sitopenia problematik gejala sistemik yg tidak terkontrol: pruritus, hiperurikemia, & penurunan BB

Manajemen terapi PV

Pengobatan

Flebotomi. Mempertahankan Ht <42% pd wanita & <45% pada laki2. Prosedur: prinsip isovolemik, & penambahan preparat Fe. Frekuensi 2-3 kali/minggu sebanyak 500 ml Usia > 65 th atau kelainan KV disertai penggantian cairan/plasma Pemeliharaan 1-2 kali/3 bulan sebanyak 500 cc

Pengobatan

Sitostatika. Hidroksiurea, chlorambusil, busulfan. Kemotrapi biologi (sitokin) dgn Interferon alfa (intron,riveron), dosis 2jt iu/m2 sc/im 3x seminggu

Fosfor radioaktif. P32 dg dosis 2-3 mCi/m2 3-4 mgg ada hasil revaluasi 10-12 mgg. Bila tidak ada hasil dosis kedua naik 25% selama 10-12 mgg.

Kemoterapi sitostatika

Indikasi: trombositosis dg bukti trombosis urtikaria berat sulit diatasi dg antihistamin. splenomegali simtomatik/mengancam ruptur lien. Hydrea: 2 x sehari 10-15 mg/ kgBB/kali. Chlorambucil (leukeran): induksi 0,1-0,2mg/kgBB/hr 36mgg, pemeliharaan: 0,4mg/kgBB/hr 2-4mgg. Busulfan (myleran): dosis 0,06mg/kgBB/hr Hentikan pengobatan bila pria ht <47%, diberikan lagi bila >52%. Pada wanita ht <42, diberikan lagi bila >49%.

Pengobatan suportif

Hiperurikemia: alopurinol 100-600 mg/hr Pruritus: dg antihistamin Gastritis: penghambat reseptor H2 Antiagregasi trombosit: anagrilide

Prognosis

Penyebab utama morbiditas & mortalitas: Trombosis (15-60%) & 10-40% penyebab kematian. Komplikasi perdarahan (15-35%) & 6-30% penyebab kematian 3-10% PV berkembang mjd mielofibrosis & pansitopenia 1,5% PV leukemia akut & MDS.

Trombositosis Esensial

Trombositosis
Definisi : kondisi peningkatan jml trombosit.

Pembagian: 1. Trombositosis klonal Trombositemia primer (esensial) MPD yg lain

2. Trombositosis familial 3. Trombositosis sekunder (reaktif) Proses transien Proses yg menetap

Trombositosis primer / klonal .Myelofibrosis .PV .CML .Metaplasia mieloid

Trombositosis

Trombositosis reaktif (sekunder) Infeksi ( meningitis,up/low tract inf, artritis, osteomyelitis) Inflamasi dan vaskulitis (rheumatoid arthritis, IBD, Henoch Schonlein purpura ) Kerusakan jaringan (post op,luka bakar) Rebound thrombocytosis (perdarahan, recovery phase of ITP, anemia deff besi) Postsplenectomy: ITP Anemia Hemolitik Keganasan Gangguan fgs ginjal

Trombositosis Esensial

Trombositosis esensial adalah kerusakan klonal stem sel multipotensial dgn ekspresi fenotip predominan pd jalur megakaryocyte-platelet tp tidak melibatkan jalur sel lainnya Prevalensi : - >> Usia > 50 thn - 10 % < 10 thn - > = 39 : 61 - Angka kejadian 400/1.000.000 populasi

Disease Transformation

ET may transform into:

Polychthemia vera (PV) Agnogenic Myeloid Metaplasia (AMM) Acute myeloid leukemia (AML) Myelofibrosis with myeloid metaplasia (MMM)

Peripheral Smear and Bone Marrow Biopsy

Diagnostic Criteria

The Polycythemia Vera Study Group (PVSG) criteria include:

A consistently elevated platelet count >600,000/ microL. Megakaryocytic hyperplasia on bone marrow aspiration and biopsy. Absence of the Philadelphia chromosome on routine cytogenetic study.

Molecular studies of the BCR/ABL gene rearrangement are now recommended to exclude cytogenetically masked cases of CML.

Diagnostic Criteria

The PSVG criteria are the gold standard for the diagnosis of ET. The World Health Organization (WHO) criteria are similar and include:
A sustained platelet count >600,000/microL. Bone marrow biopsy showing proliferation of enlarged, mature megakaryocytes. No evidence of PV, CML, chronic idiopathic myelofibrosis, myelodysplastic syndrome, or reactive thrombocytosis.

Gambaran klinis

Nyeri Baal/mati rasa Sakit kepala Erythromelalgia, acroparesthesis Thrombosis mikrosirkulasi (ggn visus, infark jari, claudicatio intermitten) Perdarahan (ekimosis, epistaksis, GIT) Splenomegali Hipertensi Abortus berulang Thrombositosis ( > 600.000/ml ) Silent

Pemeriksaan darah dan sumsum tulang

Jumlah trombosit dapat hanya sedikit meningkat di atas normal sampai beberapa juta per mikroliter Trombosit pucat kebiruan, dan hypogranular. Fragment nucleated megakaryocyte dengan gambaran lymphoblastoid kadang-kadang dapat terlihat Dapat ditemukan leukositosis ringan dan anemia ringan

Pemeriksaan darah dan sumsum tulang

Hitung jenis leukosit biasanya normal, tanpa sel-sel darah merah berinti Sumsum tulang menunjukkan peningkatan selularitas dengan hiperplasi megakariosit dan masses of platelet debris (platelet drifts).

Diagnosis
Kriteria diagnosis trombositosis esensial: Jumlah trombosit > 450.000/mm3 Penyebab lain (-) Sindr. mielodisplasia & ggn mieloproliferatif (-) Sumsum tulang : - Hiperplasi megakariositik - Fibrosis < 1/3 bagian Kriteria tambahan: Splenomegali In vitro pembentukan megakariositik spontan

Kriteria Diagnosis ET
I. Hitung platelet > 600.000/mm3

II. Hemoglobin 13 g% atau massa darah merah normal

III. Sustainable iron in marrow or failure of iron trial (<1g% rise in hemoglobin after 1 month of iron therapy) IV. Tidak terdapat Philladelphia chromosome t(9;22) V. Fibrosis Kolagen sumsum tulang Tidak ditemukan atau Kurang dari 1/3area biopsi tanpa splenomegali dan reaksi leukoerytroblastic VI. Tidak ada sebab yang diketahui untuk reaksi trombositosis
Polycythemia Vera Study Group 1986

Diagnosis Banding

Diagnosis dibuat dengan menyingkirkan diagnosis banding lainnya, karena tidak terdapat spesifik marker untuk penyakit ini: Tidak mengalami defisiensi besi & jumlah sel darah merah normal sampai rendah dgn besi yang cukup. Tidak didapatkan kromosom philadelphia Tidak ditemukan myelofibrosis Tidak ada sebab yang diketahui untuk trombositosis sekunder

Differential Diagnosis

Includes:
Reactive thrombocytosis Familial essential thrombocythemia Chronic myelogenous leukemia (CML) Polychthemia vera (PV) Agnogenic Myeloid Metaplasia (AMM)

Diagnosis banding trombositosis

Trombosis klonal Penyakit dasar Iskemia digital / serebrovask. Trombosis arteri/ vena besar Hemoragik Splenomegali Gamb Drh Tepi Fungsi trombosit Gambaran sumsum tulang Jumlah morfologi Tidak ada Karakteristik Resiko tinggi Resiko tinggi 40 % Trombosit raksasa sering abnormal Trombosis reaktif Sering Tidak ada Tidak ada Tidak ada Tidak ada Normal Normal

Meningkat Giant dysplastic form with increased playdy associated with mass of platelet debris Andrew ;NEJM 350:12. 2004

Meningkat Normal

Terapi

Sitoreduksi

perdarahan aktif & rekuren trombosis berulang sindroma iskemik mikrovaskular digital & cerebrovaskular target trombosit < 500.000 sel/ul

Tiga obat utama: - Anegrelde - Hydroksiurea (HU) - Interferon alfa

Anagrelide - Menghambat proliferasi & diferensiasi megakariosit - Dapat dijadikan terapi alternatif - Dosis mulai 2 mg/hari (terbagi dalam 2-4 dosis), dapat ditingkatkan 0,5 mg/hari setiap 7 hari sp tercapai target jumlah trombosit. Dosis maksimal 10 mg/hari - ESO: retensi cairan, palpitasi, aritmia (vasodilator & inotropik positif)

Terapi adjuvant

Agen-agen Antiplatelet : Indikasi: komplikasi trombosis berulang tu iskemik digital & serebrovaskular Memperbaiki keluhan eritromelalgia Menyebabkan perpanjangan masa perdarahan dan episode perdarahan serius Low-dose aspirin (100 mg/day) dapat memberikan respon klinik yg memuaskan KI: pasien dgn riwayat perdarahan

Penatalaksanaan ET Campbell & Green:

Pengelolaan faktor resiko KV (merokok, hipertensi, hiperkolesterolemi, obesitas) Resiko tinggi ( riwayat trombosis, >60 thn, tromb >1.500.000/mm3): aspirin dosis rendah + hidroksiurea (anagrelide & IFN pilihan kedua) Resiko menengah ( 40-60 thn): aspirin dosis rendah, pertimbangkan sitoreduktif jk ada resiko kardiovaskuler Resiko rendah (<40 thn): aspirin dosis rendah

Approach to the management of thrombocytosis

Thrombocytosis (>450.000 platelets/mm3

Clonal

Secondary (reactive)

Asymptomatic

Symptomatic

Treat underlying Disease only

Low risk

High risk (age>60 yr or Cardiovascular risk factors

>1.5 million Platelets/mm3

History of Thrombosis or bleeding

Active cerebrovascular Or digital ischemia

Follow Without treatment

Cytoreduction And aspirin

Cytoreduction only

Andrew :NEJM 350:12. 2004

Cytoreduction and (if thrombosis present) aspirin

Immediate cytoreduction & aspirin,platelet pheresis should be considered

Prognosis

Mortalitas & morbiditas disebabkan oleh trombosis dan perdarahan Konversi jadi leukemia akut, mielofibrosis atau mielodisplasia

DISSEMINATED INTRAVASCULAR COAGULATION

DIC arises from excessive activation of the coagulation cascade, followed by activation of the fibrinolytic system. Coagulation is activated in two ways: 1. Release of tissue factor from damaged tissues, monocytes or red blood cells. 2. Activation of factors XII and XI by damaged vascular endothelium.

What is DIC?

Is considered an acquired bleeding disorder Is not a disease entity but an event that can accompany various disease processes Is an alteration in the blood clotting mechanism:abnormal acceleration of the coagulation cascade, resulting in thrombosis As a result of the depletion of clotting factors, hemorrhage occurs simultaneously Is a Paradoxical Clinical Presentation clotting and hemorrhage
Nursing)

(Porth, C.M. (2004) Essentials of Pathophysiology) & (Otto, S. (2001). Oncology

Causes of DIC
1.Acute: obsteric complications, septicaemia, acute haemolysis, shock 2.Subacute: malignancy 3.Chronic: liver disease, malignancy, eclampsia.

Pathophysiology
Thrombosis-brief period of hypercoagulability 1) Coagulation cascade is initiated, causing widespread fibrin formation 2) Microthrombi are deposited throughout he microcirculatory 3) Fibrin deposits result in tissue ischemia, hypoxia, necrosis 4) Leads to multi organ dysfunction
(Porth, 2004) & (Otto, 2001)

Fibrinolysis-period of hypocoagulability (the hemorrhagic phase) 1) Activates the complement system 2) Byproducts of fibrinolysis (fibrin/fibrin degradation products(FDP)) further enhance bleeding by interfering with platelet aggregation, fibrin polymerization, & thrombin activity 3) Leads to Hemorrhage

Pathophysiology

(Porth, 2004)

Pathologic Pathways

Extrinsic (endothelial) Shock or trauma Infections ( gram positive and gram negative sepsis, aspergillosis) Obstetric complications (eclampsia, placenta abruptio, fetal death syndrome) Malignancies: APML, AML, cancers of the lung, colon, breast, prostate)
(Porth, 2004) & (Otto, 2001)

Intrinsic (blood vessel) Infectious vasculitis (certain viral infections, rocky mountain spotted fever) Vascular disorders Intravascular hemolysis (hemolytic transfusion reactions) Miscellaneous: snakebite, pancreatitis, liver disease

Diagnosis/Lab Findings
Test Platelet count Fibrin degradation product (FDP) Factor assay Prothrombin time (PT) Activated PTT Throbimn time Fibrinogen D-dimer Antithrombin Abnormality Decreased Increased Decreased Prolonged Prolonged Prolonged Decreased Increased Decreased
(Otto,2001)

Laboratory profiles in acute and chronic DIC

Acute DIC Thrombocytopenia PT Chronic DIC

Moderate to severe Mild to severe Prolonged Normal to slightly prolonged aPTT Prolonged Normal to short TT Prolonged Normal to moderately prolonged Fibrinogen Decreased Moderately decreased, normal or high Factors V and VIII Decreased Normal Protamine sulfat test Positive Positive Fibrinogen Positive Positive Degradation Products (FDP)

Clinical Features

Onset maybe Acute or Chronic

Acute DIC
Develops rapidly over a period of hours Presents with sudden bleeding from multiple sites Treated as a medical emergency

Chronic DIC
Develops over a period of months Maybe subclinical Eventually evolves into an acute DIC pattern

(Otto, 2001)

Clinical Manifestations of DIC

ORGAN Skin
Ischemic Findings are earliest!

ISCHEMIC
Pur. Fulminans Gangrene Acral cyanosis Delirium/Coma Infarcts Oliguria/Azotemia Cortical Necrosis Myocardial Dysfxn Dyspnea/Hypoxia Infarct Ulcers, Infarcts Adrenal infarcts

HEMOR.
Petechiae Echymosis Oozing Intracranial bleeding Hematuria

CNS Renal Cardiovascular Pulmonary GI Endocrine

Bleeding is the most Hemorrhagic obvious lung clinical finding

Massive hemorrhage.

Signs and Symptoms

Most common sign of DIC is bleeding Manifested by ecchymosis, petechiae,and purpura Bleeding from multiple sites either oozing or frank bleeding Cool and or mottled extremities may be noted Dyspnea and chest pain if pleura and pericardium involvement Hematuria
(Porth, 2004) & (Otto, 2001)

Differential Diagnosis

Severe liver failure Vitamin K deficiency Liver disease Thrombotic thrombocytopenic purpura Congenital abnormalities of fibrinogen HELLP syndrome

Treatment of DIC

Stop the triggering process .

The only proven treatment!

Supportive therapy No specific treatments

Plasma and platelet substitution therapy Anticoagulants Physiologic coagulation inhibitors

Treatment Modalities

Treat the underlying cause Provide supportive management of complications Support organ function Stop abnormal coagulation and control bleeding by replacement of depleted blood and clotting components (FFP,Platelets,PRBC) Medications can be used and choice depends on the patients condition (Heparin, Antithrombin III (ATIII), Fibrinolytic inhibitors)

(Porth, C.M. (2004) Essentials of Pathophysiology) & (Otto, S. (2001). Oncology Nursing)

management of underlying problem

Supportive Resuscitation Appropriate antimicrobials Eliminate source of infection

Fact: DIC usually not immediately reversed Consider anticoagulants, blood components, and coagulation inhibitors

SURGERY NOT CONTRAINDICATION

Indication and method of blood component therapy

DIC : consumption of blood components : risk of bleeding Plasma and platelets in sepsis: rational

Recommendations: Therapy according to clinical condition In general: give platelets and plasma when bleeding present or potential danger (e.g., procedures) Platelet count < 30.000/uL : prophylactic transfusion