凝血功能相關疾病的數據判讀 - mt.org.tw

凝血功能相關疾病的數據判讀

李名世

中山醫學大學醫學檢驗暨生物技術學系

中山醫學大學附設醫院檢驗科

2

References

•一般醫學實習手冊–症狀技能導向學習

•立大圖書有限公司

•臨床及診斷檢驗–合記圖書出版社

•劉奕銑(保羅)著

•Hematology for the medical student–Lippincott Williams & Wilkins

•Alvin H.Schmaier, Lilli M.Petruzzelli

3

3

Basic Sequence of Events in

Hemostasis

• Step 1:Vasoconstriction (P)

• Step 2:Platelet Adhesion (P)

• Step 3:Platelet Aggregation (P)

• Step 4:Fibrin-platelet plug Formation (S)

• Step 5:Fibrin Stabilization (S)

• (P)=primary hemostasis

• (S)=secondary hemostasis

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4

Laboratory Investigation of

Primary Hemostasis

• Platelet count

• Bleeding time

– Duke method

– Ivy method(40mmhg, 1mm wide and 3mm

deep)

– Template method(9 or 5mm wide and 1mm

deep)

• Platelet aggregation test

• Clot retraction test

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5


Secondary Hemostasis and

Fibrinolysis

• Screen tests

– Prothrombin time

– Activated partial thromboplastin time

– Thrombin time

– Interpretation of PT and aPTT

• PT normal and aPTT abnormal

• PT abnormal and aPTT abnormal

• PT abnormal and aPTT normal

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Fibrinolysis

• Confirmatory test for factor abnormalities

– Substitution aPTT and PT tests

– Factor assays

– Synthetic substrate

– Fibrinogen assay

– Factor XIII screening tests

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7



Fibrinolysis

• Tests for fibrinolysis

– FDP

• Latex agglutination

– D-dimer test

• Enzyme-linked immunosorbent assay

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Bleeding Disorders

• Pathogenesis

– Causes• Plasma protein defect

• Platelet abnormality

• Defect in platelet-endothelial cell interactions

– Coagulation protein defects• True protein deficiency

• Inhibition of an active region of a protein

• Production of an abnormal protein molecule

• Enhanced clearance of the protein

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Screening Tests for Bleeding

Disorders

• aPTT

• PT

• Platelet count

• Bleeding time

• Thrombin clotting time (TCT)

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Interpretation of Screening Tests of

the Proteins

• aPTT

– The intrinsic pathway

• PT

– The extrinsic and common pathway pathway

• TCT

– A direct measure of fibrinogen function

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Differential Diagnosis (1/2)

• Prolonged aPTT only

– Disorders associated with bleeding

• Factors VIII, XI, XII

– Disorders not associated with bleeding

• Factor XII

– A very prolonged aPTT

• PK

– A mildly prolonged aPTT

• HK

• Lupus anticoagulants

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Differential Diagnosis (2/2)

• Prolonged PT only

– Usualy

• Facctor VII

– Occasionally

• Dysfibrinogenemia

• Factors II, V, X

• Prolonged aPTT & PT

– Medical causes

– Dysfibrinogenemia-abnormal molecules

– Factors II, V, X

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Prolonged Bleeding Time

• A normal platelet count

– Von Willebrand factor

– Platelet function

– Rare connective tissue disorders

• Platelet defects

– Quantitative decrease

– True function defect

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Bleeding with no Abnormality in the

Screening Tests

• Factor XIII

– A result of surgery or trauma

• α2-Antiplasmin deficiency

• PAI-1 deficiency

• α1-AntitrypsinPITTSBURGH

15

Congenital Bleeding Disorders

• Deficiencies in

– Factor VIII (hemophilia A)

– Factor IX (hemophilia B)

– Factor XI (hemophilia C)

– vWD

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Acquired Bleeding Disorders (1/3)

• Anticoagulation

– Medications

• Heparin, Warfarin (Coumadin)

– Prolonged PT, aPTT

– Normal bleeding time

• Aspirin

– Prolonged bleeding time

– Normal PT, aPTT

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• DIC

– Bleeding or thrombosis

– Laboratory evaluation

• Screening tests

– PT, aPTT, platelet count, fibrinogen level

– Possible, probable, consider to be

• Confirmatory tests

– D-dimer assay

» insoluble

– FDP

» Soluble, insoluble

– Fibrin monomer assay

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• Liver disease

• Vitamin K deficiency

• Massive transfusion

• Uncommon acquired coagulation protein

defects

– Dyafibrinogenemias

– Inhibitor

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Platelet Disorders

• Quantitative disorders

– Thrombocytopenia

• Production

– Primary bone marrow disorders

– Bone marrow invasion

– Bone marrow injury

– Nutrition disorders

– Hereditary thrombocytopenic syndrome

• Increased destruction

• Drug induced

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Platelet Disorders

• Qualitative disorders

– Congenital

• Adhesion

• Aggregation

• Secretion

– Acquired

• Antiplatelet antibody

• Liver diseases

• Etc.

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Venous Thrombosis (1/2)

• Causes– Protein defect

• Factor V Leiden (20-40%)

• Homocysteine (10%)

• Prothrombin 20210 (6%)

• Protein C (4%)

• Protein S (3-4%)

• Dysfibrinogenemia (3%)

• Antithrombin (1%)

• Dysplasminogenemia (<1%)

• Reduced heparin cofactor II

• Elevation of PAI 1

• Elevation of Factors XI, VII, IX, VIII, X, and II

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Venous Thrombosis (2/2)

• Causes

– Hematologic diseases

• DIC

• HITTS (heparin-induced thrombosis-

thrombocytopenia syndrome)

• Antiphospholipid antibody syndrome

• TTP (thrombotic thrombocytopenic purpura)

• HUS (hemolytic uremic syndrome)

• MPD

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Risk Factors of Venous Thrombosis

• Age

• Prolonged immobility

• Obesity

• Neurologic disease

• Cardiac disease

• Pregnancy and postpartum period

• Oral contraceptives

• Surgery

• Malignancy and thrombosis

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Case Study (I)

• A 3-year-old girl was brought to her family

physician for suture (縫合) of a severe laceration

(劃破) to the left foot that resulted from stepping

on a piece of broken bottle while swimming.

Following successful closing of the wound, she

was sent home. Two weeks later, the physician

removed the stitches and observed poor wound

healing and severe dehiscence (裂開), or gaping

of the wound. There was no prior history of

bleeding problem.

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Laboratory Results

• Prothrombin time (PT): prolonged

• Thrombin time: prolonged

• Fibrinogen: 300mg/dl

• Reptilase time: prolonged more than the

TT

• Thromboelastograph: decreased tensile

strength

• Urea solubility test: abnormal

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Finding

• A defect in fibrinolysis ?

– PT, TT, fibrinogen

• A dysfibrinogenemia ?

– Fibrinogen

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Case Study (II)

• A 4-year-old boy with a history of

streptococcal pharyngitis and tonsillitis

was admitted to the hospital for a

tonsillectomy. Routine admission

laboratory work included a CBC with

normal results and

•

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Laboratory Results

• Bleeding time : 6.5 min. (2.75-8)

• Ptothrombin time: 11sec. (10-13)

• Activated partial thromboplastin time: 67

(29-42)

• Thrombin time: 20 sec. (18-25)

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Further Laboratory Results

• APTT: 65 sec.

• APTT+ fresh normal plasma: 45 sec.

• APTT+ absorbed plasma: 43 sec.

• APTT+ serum: 46.5 sec.

• Factor XI: 120% activity

• Factor XII: 98% activity

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Finding

• A Fletcher factor deficiency (prekallikrein)

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Case Study (III)

• CBC

– Hgb: 9.8 g/dl

– Hct: 31.2%

– RBC: 3.7X 106/ul

– MCV: 84.5 fl

– MCH: 26.5 pg

– MCHC: 31.8%

– WBC: 9800/ul

– D.C.

– Platelet: 32X 103/ul

• Morphology

– Moderate microcytes, few

spherocytes, few

schistocytes

• Coagulation

– PT: 12.3 sec. (control 11.6)

– aPTT: 34.5 sec. (control

32.1)

– TT: 18.5 sec. (control 21.2)

– BT: 14 min. (control 3-7.5)

• Urine

– Hgb: 2+

紅血球相關疾病的數據判讀

李名世中山醫學大學

醫學檢驗暨生物技術學系附設醫院檢驗科

33

References

•一般醫學實習手冊–症狀技能導向學習

•立大圖書有限公司

•臨床及診斷檢驗–合記圖書出版社

•劉奕銑(保羅)著

•Hematology for the medical student–Lippincott Williams & Wilkins

•Alvin H.Schmaier, Lilli M.Petruzzelli

34

Concepts

•Dynamic

–Hemostatic

• 物質不滅定律

• 監測系統

–認證之品質管理系統

• 指標

• 閾值

35

Clinical Definition of Anemia

•通常指各種原因導致的RBC細胞容量低於正常的臨床綜合症狀

•臨床常以Hb, RBC, Hct, MCV等指標表示.

•貧血是一種續發性改變, 因此病因很重要

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Anemia

• Disease?

• Symptom?

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貧血的分類(1/2)

•依發展速度

–急性貧血、慢性貧血

•依RBC細胞形態，主要參考MCV

–Macrocytic anemia

–Normocytic anemia

–Microcytic anemia

•依B.M.之RBC系增生情況

–增生性貧血

–增生不良性貧血

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貧血的分類(2/2)

•依病因、發病機制分

–RBC生成減少性貧血•造血原料異常

•造血細胞異常

•造血調控異常

–RBC破壞過多性貧血•溶血性貧血

–失血性貧血

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鑑別診斷(1/3)

•缺鐵性貧血(IDA)

•巨母球細胞性貧血(megaloblastic anemia)

•再生不良性貧血(aplastic anemia)

•純紅血球再生障礙性貧血

•骨髓增生異常綜合症, 白血病(MDS, leukemia)

•繼發性骨髓抑制

–苯, 抗癌化療藥物, 病毒感染(如EBV,HIV等)

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鑑別診斷(2/3)

•骨髓基質細胞及造血環境異常

–骨髓炎，骨髓纖維化等

•慢性病性貧血

–慢性肝病，腎功能不全，慢性感染等

•先天性RBC porphyrin 代謝異常

•地中海型貧血(thalassemia)

•葡萄糖六磷酸脫氫酶缺乏症(G6PD deficiency)

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鑑別診斷(3/3)

•遺傳性球形細胞增多症，遺傳性球形細胞增多症

•陣發性夜間血色素蛋白尿(paroxysmal nocturnal hemoglobinuria，PNH)

•免疫性溶血

•微血管性溶血

–DIC，TTP，人工瓣膜植入術後

•急、慢性失血性貧血

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Clinical Manifestation of Anemia

• 依病因

43

Laboratory Evaluation of Anemia :

Complete Blood Count (CBC)

• CBC, or automated blood count

• Measured values

– RBC quantitative information

• RBC, Hb, Hct

– RBC indices

• MCV, MCH, MCHC, RDW

44

RBC Information by CBC Data

• Ratio

– RBC

– Hb

– Hct

– MCV

• Interference

– RBC fragment, cold agglutination

– Giant platelet, platelet clumping

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Mechanisms of Anemia

• Hemorrhage

– Bleeding • Hemostatic system

• Trauma, surgery, or an underlying disease

• Gastrointestinal tract

• Menstruation

– Hemolysis• Hematologic studies

• Plasma or serum

• Urine

46

Laboratory Evaluation of Hemolytic

Anemia

• Hematologic studies

– Routine blood film

• Morphologic changes

– reticulocyte count, Bone Marrow examination

• Plasma or serum

– Bilirubin, haptoglobin, plasma Hb, LDH

• Urine

– Bilirubin, hemosiderin, Hb

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Classification of Anemia by the

Erythropoietic Response

• Elevated reticulocyte count

• Normal or decreased reticulocyte count

– Acute loss or destruction

– Vitamin or mineral deficiency

– Bone marrow depression

– Defective RBC production

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Classification of Anemia by Red

Blood Cell Size (1/3)

• Microcytosis

– MCV<80 fl

– Inherit• α-Thalassemia (deficiency in α-globin synthesis)

• β-Thalassemia (deficiency in β-globin synthesis)

• Hb E disease (a mild type of β-thalassemia)

• Sideroblastic anemia (defective heme synthesis)

– Acquried• IDA，anemia of chronic disease，lead poisoning，

medications

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• Macrocytosis

– MCV>100 fl

– Megaloblastic anemia

• MCV>110 fl with megaloblastic anemia

• Caused by impaired DNA synthessis

– Non- megaloblastic anemia

• A variety of cause

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• Normocytic anemia

– MCV (80~100 fl)

– Systemic illness

• Chronic disease

• Combined iron and vitamin B12 deficiency

– Hypoproliferative normocytic anemia

• Low reticulocyte count)

51

Classification of Anemia by

Variability in RBC Size

• RDW

– (Standard deviation of MCV / MCV) X 100

• 11.5%~14.5%

• CV

– Anisocytosis

– Conjunction with MCV

• Normal with thalassemia

• Increased with IDA

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p27

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p28

54

p32

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凝血功能相關疾病的數據判讀 - mt.org.tw