Transcript Ref. 1 - 口腔病理科教學網

口 腔 病 理 科
Diseases of blood and
blood-forming organs
血液與造血器官疾病
陳玉昆教授: 高雄醫學大學 口腔病理科
07-3121101~2755
[email protected]
學 習 目 標
Understanding:
1. Diseases of blood
2. Diseases of blood-forming organs
參考資料
Patton KT. Thibodeau GA. Anatomy & Physiology. 7th edition, St. Louis, Mosby, 2010
http://zh.wikipedia.org/wiki/File:Erythropoietin.png
Damjanov I, Lindor J. Anderson’s Pathology, 10th edition, St. Louis, Mosby, 1996
Raven PH, Johnson GB. Biology, 5th edition, NY, McGraw-Hill, 1999
2008 EdNurses, Inc.
asanagi987.blog27.fc2.com
www.mun.ca
www.lookfordiagnosis.com
Pathologyatlas.com
es.wikipedia.org
medcell.med.yale.edu
Neville BW, Damm DD, Allen CM, Bouquot JE. Oral & Maxillofacial Pathology, 3rd edition, St.
Louis, Saunders WB, 2009
13. commons.wikimedia.org
14. www.studyblue.com
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(1) Homeostasis
Composition of blood:
whole blood, plasma, proteins
Plasma
(percent by volume)
Whole Blood
(% by volume)
Protein
7%
Blood 8%
Water
92%
Plasma
55%
Other solutes
1%
Other fluids
& tissues 92%
Platelets
140,000340,000
Buffy
coat
Formed
elements
45%
Total Body Weight
Albumins 57-60%
Globulins 38%
Fibrinogen 4%
Prothrombin 1%
Other
solutes
Ions
Nutrients
Waste products
Gases
Regulatory
substances
Leukocytes
Leukocytes
5,000-10,000
Neutrophils
40-60%
Erythrocytes
4.2-6.2
million
Lymphocytes
20-40%
Monocytes
2-8%
Centrifuged
sample of
blood
Eosinophytes
2-4%
Formed elements
(No./mm3)
Homeostasis (dynamic equilibrium: 動態平衡)
Proteins
Basophils
0.5-1%
Ref. 1
(1) Homeostasis
Compensation mechanisms
1
5
Bone
marrow
6
Erythrocytes
 EPO
2
4
3
 O2
1. Decreased RBCs
2. Decreased hemoglobin synthesis
3. Decreased blood flow
4. Hemorrhage
5. Increased O2 consumption by
tissues
Kidney
9
 EPO
8
 O2
7
EPO (Erythropoietin): 紅血球生成素
Refs. 1, 2
(1) Homeostasis
Clotting cascades
Three components
- Vasculature (endothelial cells)
- Blood proteins (clotting factors)
- Platelets (vasospasm)
Basic blood clotting mechanism
- Injured tissue & activated platelets
(凝血酶)
- Chemical reactions: result in formation of thrombin
- Formation of fibrin, trapping of blood cells to form clot
cascade:級聯
(1) Homeostasis
Extrinsic
Pathway
Clotting cascades
Intrinsic
Pathway
Activated by 2 ways
Extrinsic- tissue
trauma
Intrinsic- vascular
damage
All routes lead to
initiation of Factor X
& thrombin  blood clot
Damage to
the blood
vessel
Damage to
tissue
outside the
blood vessel
Inactive
Factor X
Cascade
of clotting
factors
Tissue
Thromboplastin
Activated
Factor X
Thrombin:凝血酶
Thrombin
Prothrombin
Fibrinogen
Fibrin
Factor XIII
Blood Clot
RBCs enmeshed(捲入)
in fibrin
Injury
1
Damaged tissue cells
Extrinsic 2. Prothrombin
3
Clotting Prothrombin
activator
factors
Calcium
Blood clot
Intrinsic
Thrombin
Fibrinogen
Fibrin
Fibrin smesh
(Blood clot)
Sticky platelet
Platelet plug
Ref. 1
(1) Homeostasis
Clotting cascades
Endothelial sloughing
I. Subendothelial exposure
•
•
•
•
•
Platelets
Occurs after endothelial sloughing(塌陷)
Platelets begin to fill endothelial gaps
Promoted by thromboxane A2 (TXa2)
Inhibited by prostaglandin I2 (PGI2, prostacyclin)
Platelet function depends on many factors, esp. Ca2+
Collagen
II. Adhesion
PGI2(前列腺素): an
unstable metabolite
synthesized by arachidonate
cyclooxygenase pathway
結構 1. 為一不飽和脂肪酸
，共含20個碳 2. 必有一個
五碳環，且上圖第7、8碳
或是第12、13碳之間至少
要有一個是雙鍵
• Initiated by loss of endothelial cells, which
exposes adhesive glycoproteins such as
collagen & von Willebrand factor (vWF) in the
subendotheliuim
• vWF in plasma deposit on the damaged areas
• Platelets adhere to subendothelium through
receptors that bind to the adhesive
glycoproteins (GPIb, GPIa/IIa, GPIIb/IIIa)
III. Activation
• After platelets adhere, they are activated to
have a conformational change in GPIIb/IIIa
receptors, resulting in their ability to bind
adhesive proteins, including fibrinogen & vWF
• Changes in platelet shape
• Formation of pseudopods
• Activation of arachidonic pathway
Sticky
platelets
Collagen
ACTIVATION
Collagen
Collagen
Platelets
Collagen
Ref. 1
(1) Homeostasis
Clotting cascades
RBC
IV. Aggregation
• Induced by release of TXa2
• Adhesive glycoproteins bind simultaneously to
GPIIb/IIIa on two different platelets
• Stabilization of the platelet plug (blood clot)
occurs by activation of coagulation factors,
thrombin, & fibrin
• Heparin neutralizing factor enhances clot formation
Platelets
Fibrin
mesh
Fibrin Thrombin
V. Platelet plug formation
• RBCs and platelets enmeshed(捲入)in fibrin
Platelet plug (blood clot)
VI. Clot retraction & dissolution
• Clot retraction, using large number of platelets,
joins the edges of the injured vessel
• Clot dissolution is regulated by thrombin and
plasminogen activators
Fibrin degradation
Plasmin
Thrombin
Plasminogen
activators
Activated protein
Thrombin:凝血酶
Ref. 1
(1) Homeostasis
Normal destruction of RBCs
Old RBCs
- Sequestered(隔離) & destroyed in spleen
- In liver- if no spleen
- Globin chains- broken down  amino acids
- Reduced to bilirubin  liver & secreted in bile
Aging-RBCs replaced more slowly
- Iron depletion(消耗)
-  total serum iron, iron-binding capacity, and
intestinal iron absorption
Lymphocyte function decreases
Bilirubin(膽紅素): an orange-yellow pigment formed in liver by breakdown
of hemoglobin & excreted in bile
(1) Homeostasis
Scanning Electron Microscope
Engulfment of RBCs by macrophage
低倍
中倍
高
倍
R: RBC
P: pseudopod
M: macrophage
Ref. 1
(2) Anemia
Generalized introduction (1)
Classified by:
- Size of RBC
Macrocytic, microcytic, normocytic
- Hemoglobin content
Normochromic, and hypochromic
Symptoms based on severity & compensation
Classic symptoms
- Fatigue, weakness, dyspnea(呼吸困難), and
pallor(蒼白)
(2) Anemia
Generalized introduction (2)
2,3-diphosphoglycerate
(2,3-DPG):
binds with great
affinity to deoxygenated
HB,  the release of
the remaining O2 2
bound to the Hb
Etiologic events
(erythropoiesis)
(blood loss)
(destruction)
Red blood cells, hemoglobin
(anemic condition)
Claudication
(跛行)
(muscle)
Respiratory
(respiratory rate, depth,
exertional dyspnea))
Pallor (skin/
mucous membrane)
1
Liver
(fatty changes, fatty
changes can also occur
in heart and kidney)
Tissue hypoxia
Weakness
(Fatigue)
2,3DPG
2
Oxygen-carrying capacity
(hypoxemia)
Ischemia
1
Central nervous system
(dizziness, fainting,
lethargy)(頭暈，昏厥，嗜睡)
Compensatory
mechanisms
Heart
(angina)
Heart rate
Oxygen demands
for work of heart
Capillary
dilation
Cardiovascular
SV
Diastolic
volume
Renal
DPG in cells
Renin-aldosterone
response
Salt and H2O
retention
Extracellular fluid
Erythropoietin
Extracellular
fluid
Hyperdynamic
circulation
Stimulates
bone marrow
Cardiac
murmurs
High-output
cardiac failure
Release of oxygen
from hemoglobin in tissues
Ref. 1
(2) Anemia
Classification
Macrocytic normochromic (megaloblastic)
- Pernicious, folate (vitamin B12) deficiency
Macrocytic, microcytic, normocytic
Microcytic hypochromic
- Iron deficiency, sideroblastic(鐵粒幼細胞),
Thalassemia (Mediterranean)
Normocytic normochromic
- Aplastic, hemolytic,
sickle(鐮刀型) cell
"hair-on-end" appearance
Ref. 12
(2) Anemia
Causes (1)
ANEMIAS WITH DISTURBED IRON METABOLISM
- Iron deficiency anemia
- Sideroblastic anemia
MEGALOBLASTIC ANEMIAS
- Cobalamin (B12) deficiency (pernicious anemia)
- Folic acid deficiency
DISORDERS OF HEMOGLOBIN
- Sickle cell anemia
- Thalassemia
(2) Anemia
Causes (2)
ANEMIAS ASSOCIATED WITH CHRONIC
DISORDERS
- Anemia of chronic infection (infective
endocarditis, osteomyelitis, lung abscess,
pyelonephritis)
- Anemia of inflammatory connective tissue
(rheumatoid arthritis, lupus erythematosus,
sarcoidosis, temporal arteritis, regional enteritis)
- Anemia associated with malignancy
- Secondary to chronic bleeding
- Myelophthisic anemia
- Anemia of uremia
- Anemia of endocrine failure
- Anemia of liver disease
(2) Anemia
Causes (3)
HEMOLYTIC ANEMIAS
- Extrinsic causes
- Splenomegaly
- Red cell antibodies
- Trauma in the circulation
- Direct toxic effects (various microorganisms,
copper salts, venom of some snakes)
- Membrane abnormalities
- Spur cell anemia(刺激細胞性貧血)
- Paroxysmal nocturnal hemoglobinuria
(陣發性睡眠性血紅蛋白尿)
- Hereditary spherocytosis(球形紅細胞增多症)
- Hereditary elliptocytosis
- Disorders of the interior of the red cell
- Defects in the Embden-Meyerhof pathway
- Defects in the hexose monophosphate shunt
(2) Anemia
Physiologic response & Compensatory
Physiologic response to anemia
- Reduced oxygen-carrying capacity of blood
- Tissue hypoxia
Compensatory
- Increase in plasma volume
- Thinner blood
- Increased blood flow
- Increased heart rate and stroke volume
- Cardiac and pulmonary symptoms
- Increased rate and depth of breathing
- Short of breath and dizziness(頭暈)
(2) Anemia
Iron deficiency- Generalized introduction
Most common form
Populations at risk
- Individuals living in poverty, women of
childbearing age, children
- Inadequate iron intake
- Poor dietary conditions & malnutrition
- Increased heart rate and stroke volume
- Increased demand for iron during infancy &
pregnancy
(2) Anemia
Iron deficiency anemia- Manifestation
Bleeding that results in iron loss- usually gradual
& occult (e.g., peptic ulcers, colonic tumors),
menorrhagia
Manifestations
- Pallor, ineffective erythrocytes
- Generalized anemia S/S
- Brittle and malformed nails
- Neurologic symptoms (e.g., numbness,
paresthesia, headache, confusion)
(2) Anemia
Sickel cell anemia- Generalized introduction
Inherited types of hemolytic anemia
Autosomal recessive- abnormality in hemoglobin
synthesis
U.S.  African-Americans
Worldwide- Mediterranean South America
India- natural protective adaptation against
malaria(瘧疾)
Slight "hair-on-end" appearance
Ref. 12
(2) Anemia
Sickel cell anemia- Two major forms
Sickle cell trait- one defective gene (heterozygous)
- Often asymptomatic (carrier) or experience
recurrent episodes associated with pain and
tissue ischemia
Sickle cell anemia- defective gene from both
parents (homozygous), has disease
- Life threatening, pain crises, organ infarction,
profound destruction of erythrocytes
(aplastic crisis)
Ref. 13
(2) Anemia
Sickle cell trait- 1 defective gene (heterozygous)
未患病
(carrier)
(Father)
未患病
(1/4機率)
未患病
(carrier)
(Mother)
未患病(carrier)
(2/4機率)
if only 1 allele is affected
(carrier), only 40-50% Hb
is abnormal
患病
(1/4機率)
Ref. 14
(2) Anemia
Sickel cell anemia- Cell morphology
(低氧血症)
Hypoxemia
Cell changes shape,
releases heme, and
becomes stiff-and-curved (sickle)
Hemoglobin “lines up”
and changes the
shape of the RBC
Ref. 1
(2) Anemia
Sickel cell anemia- Sickle cell
Normal red cell
Siickel cell
Point
Macrophage
mutation
Splenic cord
Valine
Glutamic acid
Endothelium
infection
HbS
HbA
Sinusoid
HbS solution
HbS polymers
Oxygenated
Deoxygenated
Infarct (e.g. bone marrow)
Irreversibly
sickled
Reversibly sickled
Membrane changes
increased adhesiveness
Spleen  Hemolysis, congestion,
infarction
Infarct (e.g. lung)
Transudation(滲出) of
inflammation fluid
Increased RBC transit
mess in inflammed tissues
Cell adhesion
Microvascular occlusion
by sickle cells
Microvascular occlusion
by sickle cells
Sickled erythrocytes: more fragile than normal & block capillaries
because of their shape & adherence properties
Ref. 14
(2) Anemia
Sickle cell anemia- Sickle cell crisis
Dehydration
Stress or strenuous(費勁) exercise
Infection
Fever
Bleeding
Acidosis
Hypoxia (smoking)
Cold weather
Pregnancy
(2) Anemia
Sickle cell anemia- Presentation
Bone crisis
Acute chest syndrome (vaso-occlusive crisis of
the pulmonary vasculature; commonly manifests
with pulmonary infiltrate on a chest x-ray)
Abdominal crisis
Joint crisis
Bleeding
Jaundice(黃疸), bruising(瘀傷) , blood in urine
Jaundice: yellowing of the skin or whites of the eyes, arising from excess
of the pigment bilirubin and caused by obstruction of the bile duct, by liver
disease, or by excessive breakdown of red blood cells.
(2) Anemia
Pernicious anemia- Generalized introduction
Most common type of macrocytic anemia
Caused by vitamin B12 deficiency and underlying
absence of intrinsic factor
- Enzyme required for gastric absorption of
vitamin B12
- Vitamin B12 required for DNA synthesis
- Congenital, autoimmune
- Bariatric(減肥) surgery patients at risk due to
gastrectomy- removal of parietal cells(胃壁細胞:
secrete HCl & an intrinsic factor that forms a
compound with vitamin B12)
Refs. 10, 11
(2) Anemia
Hemolytic anemia- Generalized introduction
Acquired- infection, systemic, liver, kidney
disease, toxins
Hemolysis
- Hemolysis of RBCs
Splenomegaly, jaundice from RBC destruction
(3) Myeloproliferative RBC
disorders
Generalized introduction
Polycythemia (abnormally increased Hb conc.
through either reduction of plasma volume or
increase in RBC no.)(紅血球增多症)
Relative polycythemia
- Result of dehydration/fluid loss
- Blood is viscous, hypercoagulable, thrombi
Absolute polycythemia
- Secondary EPO (Erythropoietin): 紅血球生成素
* Increase in EPO to chronic hypoxia or
response to EPO-secreting tumors
(4) WBC disorders
Generalized introduction
Leukocytosis (白血球增多)
- Normal protective physiologic response to
physiologic stressors
Leukopenia
- Leukopenia is not normal and not beneficial
- Low WBC predisposes to infection
(4) WBC disorders
Granulocyte disorders- Classification
Granulocytopenia (agranulocytosis)
- Hematopoiesis, immune mechanisms, chemo &
radiation
Granulocytosis (neutrophilia)
- 1st stages of infection/inflammation
- Demand beyond supply- immature neutrophils
(bands)
- WBC differential = termed a “shift to the left”
Neutropenia
- Reduction in circulating neutrophils
- Causes
* Prolonged severe infection
* Decreased production
* Abnormal distribution & sequestration
(4) WBC disorders
Granulocyte disorders- WBC differential
Normal WBC Count 4,000 – 10,000 cells/mL
Bands
Neutrophils
<1% 55%
Lymphocytes Monocytes Eosinophils Basophils
36%
3-8% 1-4% 0.5%
WBC elevated with bacterial infection
“Shift to left” – increase in bands & neutrophils
Bands
5%
Neutrophils
75%
Lymphocytes Monocytes Eosinophils Basophils
12%
4%
3%
0.3-0.5%
Bands: immature neutrophils
Ref. 1
(4) WBC disorders
Leukemia- Introduction & classification
Malignant disorder of blood & blood-forming
organs
Excessive WBC proliferation
Based- cell of origin
- Myeloid(骨髓)
- Lymphoid(淋巴)
Manifestations
- Anemia, petechiae(瘀斑), ecchymosis(瘀斑),
thrombosis, hemorrhage, DIC (disseminated
intravascular coagulation ), infection, weight
loss, bone pain, liver, spleen, lymph node
enlargement, pancytopenia (deficiency of all 3
cellular components of blood (RBCs, WBCs, &
platelets), fatigue
(4) WBC disorders
Acute leukemia- Generalized Introduction
Acute: rapid growth of immature/undifferentiated
blood cells (blast cells)
Onset rapid & abrupt
 survival time- 85% B-cells, 50% over 50 years of
age
(4) WBC disorders
Acute leukemia- Classification
Acute lymphocytic leukemia (ALL)
- Least common overall– common in children(78%)
 Acute myelogenous leukemia (AML)
- More common in adults
- 20% survival rate
(4) WBC disorders
Chronic leukemia- Generalized Introduction
Chronic- slow growth of more differentiated/
mature cells
Do not function normally
Gradual onset
Longer disease course
Longer survival time, mostly 60-80 years old
Arise from many different mature WBCs
(4) WBC disorders
Chronic leukemia- Classification
Chronic lymphocytic leukemia (CLL)
- More commonly in children
- 73% survival rate
Chronic myelogenous leukemia (CML)
- Mostly adults
(4) WBC disorders
Leukemia- Summary
Pluripotential stem cell
Acute undifferentiated leukemia
Lymphoid stem cell
Acute lymphocytic leukemia
(ALL)
Chronic lymphocytic
leukemia, nonHodgkin lymphoma
(CLL)
T cell
B cell
Acute erythroleukemia
Erythroid stem cell
Chronic myelogenous
leukemia
Erythrocyte
Acute megakaryocytic
leukemia
Megakaryocytic
stem cell
Acute myelogenous
leukemia (AML)
Granulocytic
stem cell
Promonocyte
Chronic myelogenous
leukemia
(CML)
Megakaryocyte
Monocyte
Polycythemia,
chronic myelogenous
leukemia
Eosinophil
Multiple Solitary
myeloma plasmacytoma
Platelet
Myeloblast
Basophil
Promyelocyte
NonHodgkin
lymphoma
Plasma cell
Humoral immunity (antibody)
IgG, IgM, IgA, IgD, IgE
Cell-mediated immunity,
graft vs host response
Myelocyte
Metamyelocyte
Segmented neutrophil
Ref. 1
(4) WBC disorders
Leukemia- Etiologies
Genetic aberrations
- Translocations (Philadelphia chromosome in
95% CML and 30% adults with ALL)
- Errors in protein
Certain hereditary tendencies:
- Down syndrome & immune deficiencies
Environmental factors:
- Cigarette smoke
- Ionizing radiation
- Cancer treatments, other cancers
- HIV, hepatitis C
- Drugs
(4) WBC disorders
Leukemia- Philadelphia translocation
Changed
Chromosome 9
Normal
Chromosome 9
Normal
Chromosome 22
BCR (q11)
(q34)
ABL
Chromosomes
break
Changed
Chromosome
22
(Philadelphia
chromosome)
BCR-ABL
Ref. 7
(4) WBC disorders
Lymphoid disorders- Types
Lymphocytosis
- Acute viral infections
Lymphocytopenia
- Immune deficiencies, drug destruction, viral
destruction
Malignant lymphomas
- Malignant transformation of a lymphocyte in
lymphoid tissues
- Two major categories
* Hodgkin lymphoma(有Reed-Sternberg cell)
* Non-Hodgkin lymphoma(無Reed-Sternberg cell)
Ref. 8
(4) WBC disorders
Hodgkin lymphoma (Reed-Sternberg cell)
Refs. 8, 9
(4) WBC disorders
Lymphoid disorders- EM photo
Ref. 4
(4) WBC disorders
Non-Hodgkin lymphoma- Generalized Introduction
Diverse group of lymphomas
- Based on etiology, features, and response to
therapies
Linked to:
- Chromosome translocations
- Viral & bacterial infections, environmental
- Immunodeficiencies, autoimmune
- Clonal expansion of B cells, T cells, and/or NK
(natural killer) cells
- Changes in proto-oncogenes and tumorsuppressor genes   malignant cells
(4) WBC disorders
Multiple myeloma- Generalized Introduction
B-cell cancer
~ 60 years old males, blacks 2 times > whites,
~ 17000 cases yearly
Infiltrates bone marrow and aggregate into tumor
masses in skeletal system
Hypercalcemia, renal failure, bone lesions
(4) WBC disorders
Lymphadenopathy- Generalized Introduction
Enlarged lymph nodes- palpable/tender
Local
- Drainage of inflammatory lesion located near
enlarged node
General
Ref. 12
(5) Splenic disorders
Splenomegaly- Generalized Introduction
Splenomegaly
- Idiopathic
- Sign of underlying disease
- Hypersplenism: overreactive splenic function
- Causes:
* Inflammation, infection, congestive disorders,
tumors or cysts
- Clinical signs
* Splenic sequestering of RBCs, WBCs and
platelets lead to anemia, leukopenia,
thrombocytopenia
(5) Splenic disorders
RBCs in the spleen
Ref. 1
(6) Platelets disorders
Generalized Introduction
Acquired (common)/congenital
- Drugs: heparin (肝素〔抗凝血藥〕), ASA
(aspirin 抗凝血 ), NSAIDS (non-steroidal antiinflammatory drugs)
- Systemic conditions: Chronic renal disease,
liver disease, iron & foliate deficiencies,…
- Heme alteration: leukemia, …
Alteration of platelet function
- Factor deficiencies (glycoprotein & von
Willebrand)
- Petechiae(瘀斑), purpura(紫癜), mucosal
bleeding, gingival bleeding, & spontaneous
bruising(瘀傷)
(6) Platelets disorders
Types and Causes
Primary thrombocythemia(血小板增多症)
- Platelet counts > 600,000
- Disorder of platelet precursor cells
(Megakaryocytes)
- Microvasculature thrombosis
Thrombocytopenia(血小板減少)
- Platelet counts < 150,000/mm3
* < 50,000 minor trauma
* < 10,000 severe bleeding
Causes
- Hypersplenism, autoimmune, hypothermia, viral
or bacterial infections causing DIC, druginduced (HIT) & idiopathic
(6) Platelets disorders
Thrombocytopenia- Clinical picture
Ref. 1
(7) Alterations of coagulation
Causes
Vitamin K deficiency
- Synthesis & regulation of prothrombin,
prothrombin factors (II, VII, XI, X), and proteins C
and S (anticoagulatents)
Liver diseases
- Liver disease causes many hemostasis
disorders
* Defects in coagulation, fibrinolysis, and platelet
number and function
(7) Alterations of coagulation
Types
Hemophilia
- Group of sex-linked recessive disorders that
cause insufficient production of clotting factors
Von Willebrand disease
- Caused by a factor VIII deficiency (inherited)
autosomal dominant disorder
TYPE
Hemophilia A (classic hemophilia)
Hemophilia B (Christmas disease)
von Willebrand's disease
DEFECT
Factor VIII deficiency
Factor IX deficiency
Abnormal von Willebrand's factor,
abnormal platelets
INHERITANCE
X-linked recessive
X-linked recessive
Autosomal dominant
FINDINGS
Abnormal PTT
Abnormal PTT
Abnormal BT, abnormal
PTT
B: Bleeding lime: PTT: partial thromboplastin time
Ref. 12
(8) Disseminated intravascular
coagulation (DIC)
Generalized introduction (1)
Complex disorder of clotting & hemorrhage
- Endothelial damage  primary initiator (tissue
thromboplastin)
- Release of thrombin with fibrin formation &
fibrinolysis (clotting)
- Thrombin exceeds the body’s anti-thrombins
- Widespread thromboses  ischemia, infarction,
organ hypoperfusion
(8) Disseminated intravascular
coagulation (DIC)
Generalized introduction (2)
Clotting factors consumed & fibrinolytic system
(plasmin) activated  bleeding
High mortality rate
Treatment  remove stimulus/supportive
- Obstetrical causes
- Cancers & hematologic conditions
- Infections
- Shocks
- Trauma/surgery
(8) Disseminated intravascular
coagulation (DIC)
Generalized introduction (3)
Platelets
Perfusion
(灌注)
Initiation
Clotting
Bleeding
Ref. 5
(8) Disseminated intravascular
coagulation (DIC)
Signs & symptoms
Bleeding:
- Occult
- Frank
Clotting:
- Venous thromboembolism (VTE, 血栓栓塞)
- Myocardial infarction (MI), pulmonary embolism
(PE), cerebral vascular accident (CVA,腦中風)
Ischemia(缺血)
Organ dysfunction
(8) Disseminated intravascular
coagulation (DIC)
Clinical picture
Ref. 1
(8) Disseminated intravascular
coagulation (DIC)
Diagnostic tests
Diagnostic tests:
- Platelets
- PT (prothrombin time前凝血酶時間)/ PTT (partial
thromboplastin time部分凝血激素時間)
- Fibrin degradation products (FDP): fibrin及
fibrinogen二者被plasmin分解的產物
- D-dimer (專指 fibrin 被分解後的片斷，保留有纖維
蛋白單體 (fibrin monomer) 中 chain 的交錯分子
結構 (cross-linked)。fibrin才有，fibrinogen
則無，D-Dimer是唯一由fibrin分解後的產物): 血中
D-Dimer增加  (1) 血中發生了fibrin 凝集; (2) 體內
抗凝血機制已啟動，已有 fibrin被切割分解
- Liver function tests
(8) Disseminated intravascular
coagulation (DIC)
D-dimer
FDP: Fibrin degradation products
Ref. 6
(8) Disseminated intravascular
coagulation (DIC)
Treatment
Treat Underlying Disorders
Able
Unable
Heparin
Replace Blood Products
Summaries
Knowing:
1. Diseases of blood
2. Diseases of blood-forming organs