BLOOD【血液】
Qiang XIA (夏强), PhD
Department of Physiology
Room C518, Block C, Research Building, School of Medicine
Tel: 88208252
Email: xiaqiang@zju.edu.cn
Internal environment （内环境）
Body Fluid = 60% of Body Weight (BW)
Plasma 5% of BW
Extracellular Fluid
1/3, 20% of BW
Interstitial Fluid
15% of BW
70 kg Male, 42 L
Intracellular Fluid
2/3, 40% of BW
Plasma 5% of BW
Extracellular Fluid
1/3, 20% of BW
Internal Environment
Interstitial Fluid
15% of BW
Homeostasis（稳态）
Homeostasis (from the Greek
words for “same” and “steady”):
maintenance of static or
constant conditions in the
internal environment
Walter B. Cannon
http://www.harvardsquarelib
rary.org/unitarians/cannon_
walter.html
Components of Homeostasis:

Concentration of O2 and CO2

pH of the internal environment

Concentration of nutrients and waste products

Concentration of salt and other electrolytes

Volume and pressure of extracellular fluid
How is homeostasis achieved?
----Regulation
Body's systems operate together to
maintain homeostasis:
Skin system
Skeletal and muscular system
Circulatory system Respiratory system
Digestive system
Urinary system
Nervous system
Endocrine system
Lymphatic system
Reproductive system
Components of blood
 Plasma（血浆）
 Blood Cells
 Red Blood Cells (RBC) or Erythrocytes（红细胞）
 White Blood Cells (WBC) or Leucocytes（白细胞）
 Platelets (PLT) or Thrombocytes（血小板）
Plasma includes
water, ions, proteins,
nutrients, hormones,
wastes, etc.
The hematocrit（血细胞比容） is a
rapid assessment
of blood composition.
It is the percent of the
blood volume that is
composed of RBCs
(red blood cells).
Hematocrit（packed cell volume, 血细胞比容）
the volume of red blood cells as a percentage of
centrifuged whole blood
M: 40~50%
F: 37~48%
International Council for Standardization in Haematology (ICSH)
Recommendations for "Surrogate Reference" Method for the Packed Cell Volume
Physical & chemical properties of blood
1. Specific Gravity（比重）
Depending on hematocrit & protein composition
Whole blood：
1.050~1.060
Plasma：
1.025~1.035
Red blood cells：
1.090
2. Viscosity（粘度）
 relative viscosity of whole blood 4~5
depending on hematocrit
 relative viscosity of plasma 1.6~2.4
related to the protein composition of the plasma
3. Osmotic Pressure（渗透压）
 The osmotic pressure of a solution
depends on the number of solute
particles in the solution, NOT on
their chemical composition and size
 Plasma osmotic pressure (~300 mOsm/L）
 Crystalloid Osmotic Pressure（晶体渗透压）
 Pressure generated by all crystal substances, particularly
electrolytes
 Important in maintaining fluid balance across cell
membranes
 Colloid Osmotic Pressure（胶体渗透压）
 Osmotic pressure generated by plasma proteins, particularly
albumin.
 Approximately 25 mmHg, but important in fluid transfer
across capillaries
4. Plasma pH
 Normal range: 7.35~7.45
 Buffer systems（缓冲系统）:
NaHCO3/H2CO3, Pro-Na/Pro, Na2HPO4/NaH2PO4
Hb-K/Hb, HbO2-K/HbO2, K2HPO4/KH2PO4, KHCO3/H2CO3
Functions of blood
 Transportation
 O2 and CO2
 Nutrients (glucose, lipids, amino acids)
 Waste products (e.g., metabolites)
 Hormones
 Regulation
 pH
 Body temperature
 Protection
 Blood coagulation
 Immunity
Plasma
Body Fluid = 60% of Body Weight (BW)
Plasma 5% of BW
Extracellular Fluid
1/3, 20% of BW
Interstitial Fluid
15% of BW
70 kg Male, 42 L
Intracellular Fluid
2/3, 40% of BW
 Composition
Water (92% of plasma)
serves as transport medium; carries heat
Proteins (6~8% of plasma)
Inorganic constituents (1% of plasma)
e.g., Na+, Cl-, K+, Ca2+…
Nutrients
glucose, amino acids, lipids & vitamins
Waste products
e.g., nitrogenous wastes like urea
Dissolved gases
O2 & CO2
Hormones
 Plasma proteins
•Albumins （白蛋白）(60-80% of plasma proteins)
•most important in maintenance of osmotic balance
•produced by liver
•Globulins （球蛋白）(1-, 2-, -, -)
•important for transport of materials through the blood (e.g.,
thyroid hormone & iron)
•clotting factors
•produced by liver except -globulins which are immunoglobulins
(antibodies) produced by lymphocytes
•Fibrinogen（纤维蛋白原）
•important in clotting
•produced by liver
Red blood cells (Erythrocytes)
（红细胞）
Structure
 Biconcave
 No nucleus
 Few organelles
 Small
 Hemoglobin molecules
 Count
RBC count
M: 4.0~5.5×1012/L
F: 3.5~5.0×1012/L
Hemoglobin（血红蛋白）
M: 120~160 g/L
F: 110~150 g/L
 Physiological
Plastic deformability
（可塑变形性）
properties
d
Suspension stability（悬浮稳定性）
Erythrocyte Sedimentation Rate (ESR)（红细胞沉降率）
 The distance that red blood cells settle in a tube of blood in one
hour
 Normal value [Westergren method（魏氏法，国际血液学标准化委员
会推荐魏氏法为标准法）]:
M: 0~15 mm/h，F: 0~20 mm/h
 An indication of inflammation which increases in many diseases,
such as tuberculosis & rheumatoid arthritis…
International Council for Standardization in Haematology (ICSH)
红细胞叠连（Rouleaux formation）
Osmotic fragility （渗透脆性）
the susceptibility of a red blood cell to break apart when
exposed to saline solutions of a lower osmotic pressure
than that of the human cellular fluid
Notice that hemolysis begins in the 0.45% tube and is complete in the 0.35% tube.
Only substances which act as impermeant molecules can
be used to make isotonic solutions （等张溶液）. E.g.
cells placed in an isosmotic solution （等渗溶液） of urea
(1.9%), a permeant molecule, will swell and bust.
Solutions which have the same calculated osmotic
pressure are said to be ISOSMOTIC but are not
necessarily ISOTONIC
 Function
of RBCs
1. Transport of O2 and CO2
2. Buffering
 Production
of RBC (Erythropoiesis)
 Hemocytoblast stem cell
 Stem cell becomes committed
 Early erythroblasts have ribosomes
 Erythroblasts accumulate iron and hemoglobin
 Normoblasts eject organelles
 Released as erythrocyte
 Nutritional Requirements for Erythropoiesis
1. Many vitamins, minerals, and proteins are necessary for normal
RBC production
2. Clinically, folic acid（叶酸）, VitB12, and iron （铁） are the
most important.
Deficiencies of these factors lead to characteristic anemias（贫血）
Diagram of iron kinetics from iron stores to developing red blood cell (RBC). Iron stores include the bone marrow, reticuloendothelial system
(liver and spleen) and RBCs. Transferrin (total iron-binding capacity [TIBC]) transports iron (Fe) to developing erythrocytes. Iron is deposited in
the RBC, and transferrin returns to storage sites to bind more Fe for transport. Lactoferrin is a competitor of transferrin; it takes Fe that is free
and returns it to storage sites. Lactoferrin levels are elevated in anemia of chronic disease. Increases in interleukin-1 increase the sequestration of
Fe in storage sites. (Hb=hemoglobin)
 Regulation
of Erythropoiesis
1. Erythropoietin（促红细胞生成素）
2. Hormones:
Androgen（雄激素）
Others
Hypoxia-inducible factor1, HIF-1
Erythropoiesis is
hormonally regulated:
decreased oxygen
delivery to the kidney
causes the secretion of
erythropoietin, which
activates receptors in
bone marrow, leading to
an increase in the rate of
erythropoiesis.
 Destruction



of RBC
Macrophages engulf old RBCs
Iron is salvaged
Heme degrades into bilirubin
average lifespan = about 120 days
Anemia（贫血）
 Anemia is defined as a qualitative or quantitative
deficiency of hemoglobin, a protein found inside
red blood cells (RBCs)
 The three main classes of anemia：
 excessive blood loss (acutely such as a
hemorrhage or chronically through low-volume loss)
 excessive blood cell destruction (hemolysis)
 deficient red blood cell production (ineffective
hematopoiesis)
Iron deficiency anemia
（缺铁性贫血）
巨幼红细胞性贫血（megaloblastic anemia）
Hemolysis（溶血）
Red blood cells without (left and middle) and with (right)
hemolysis. Note that the hemolyzed sample is transparent,
because there are no cells to scatter light.
White blood cells (Leucocytes)
（白细胞）
 Types
of WBC
 WBC
WBC
Granulocytes
Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes
Total
count
Count (109/L)
2.0~7.0
0.02~0.5
0~0.1
0.12~0.8
0.8~4.0
50~70
0.5~5
0~1
3~8
20~40
4~10
%
Leukopoiesis
 Myeloblasts become all of the granular leukocytes
 Monoblasts become monocytes
 Lymphoblasts become lymphocytes
Platelets
(Thrombocytes)





Formed in the bone marrow
from cells called
megakaryocytes
Without nucleus, but can
secrete a variety of
substances
normal value:
(100~300) x 109/L
Average lifespan=7~14 days
Play an important role in
hemostasis
 Physiological
properties of platelets
1. Adhesion
Platelets adhere to the vessel wall at the site of injury
von Willebrand factor, vWF
Unifying model of platelet adhesion to collagen at arterial shear. Two different pathways by which human and mouse platelets firmly
adhere to collagen at arterial shear are illustrated. In both, the majority of platelets are initially tethered to collagen via GP Ib/IX/V
interacting with collagen-bound VWF (left), although a minority of platelets interact directly with collagen independently of VWF/GP
Ib/IX/V. In the first pathway (upper), signaling from GP VI first leads to activation of integrins α2β1 (GP Ia/IIa) and αIIbβ3 (GP IIb/IIIa).
Activated integrins then firmly attach the platelet to collagen, either directly (α2β1) or via collagen-bound VWF (αIIbβ3) (right). In the
second pathway (lower), platelets first adhere to collagen via integrin α2β1, before GP VI engages collagen and induces activation.
These two pathways are likely to reinforce each other and the events of thrombus formation. Release of secondary mediators (ADP and
TxA2) would further potentiate these events (right). (Redrawn from Auger JM, Kuijpers MJ, Senis YA: Adhesion of human and mouse
platelets to collagen under shear: a unifying model. FASEB J 2005;19:825-827.)
2. Aggregation
Platelets adhere to one another
Platelet Aggregation Pathway
Platelet activation and coagulation normally do not occur within an intact blood
vessel. After vessel wall injury, platelet-plug formation is initiated by the
adherence of platelets to subendothelial collagen. In high shear arterial blood,
platelets are first slowed down from their blood flow velocity by interacting with
the collagen-bound von Willebrand factor (VWF) and subsequently stopped by
binding directly to collagen via their glycoprotein receptor complex. The
activation of these collagen receptors on platelets following their binding to
collagen activates phospholipase C (PLC)-mediated cascades. This results in
a mobilization of calcium from the dense tubula system. An increase in
intracellular calcium is associated with activation of several kinases necessary
for morphological change, the presentation of the procoagulant surface, the
secretion of platelet granular content, the activation of glycoproteins, and the
activation of Phospholipase A2 (PLA2). Activation of PLA2 releases
arachidonic acid (AA), which is a precursor for TBXA2 synthesis. PTGS1
catalyzes the first step in the formation of TBXA2 from AA. This reaction is
irreversibly blocked by aspirin, which also leads to the blockage of platelet
aggregation
These processes result in the local accumulation of molecules like thrombin,
TBXA2, and ADP, which are important for the further recruitment of platelets
as well as the amplification of activation signals as described above. The
secreted agonists activate their respective G protein coupled receptors:
thrombin receptor (F2R), thomboxane A2 receptor (TBXA2R), and ADP
receptors (P2RY1 and P2RY12). The P2RY12 receptor couples to Gi, and
when activated by ADP, inhibits adenylate cyclase. This interaction
counteracts the stimulation of cAMP formation by endothelial-derived
prostaglandins, which alleviates the inhibitory effect of cAMP on IP3-mediated
calcium release. Thienopyridines, a class of oral antiplatelet agents,
permanently inhibit P2RY12 signaling, which is sufficient to block platelet
activation.
F2R, TBXA2R and P2RY1 couple to the Gq-PLC-IP3-Ca2+ pathway, inducing
shape change and platelet aggregation. In addition, receptor signaling through
G12/13 (F2R; TBXA2R) contributes to morphological changes through
activation of kinases.
Platelet adhesion, cyotoskeletal reorganization, secretion, and amplification
loops are all different steps towards the formation of a platelet-plug. These
cascades result in the activation of the Fibrinogen Receptor expressed on
platelet cells. This activation develops binding sites for fibrinogen, which are
not available in inactive platelets. The binding of fibrinogen results in the
linkage of activated platelets through fibrinogen bridges, thereby mediating
aggregation. Inhibition of this receptor through Glycoprotein IIb/IIIa inhibitors
blocks platelet aggregation induced by any agonist.
 Inducers of platelet aggregation
 ADP
 Low dose 1st reversible phase
 High dose
2nd irreversible phase
 Thromboxane A2 (TXA2)
 Collagen
 Thrombin
Phospholipid
Phospholipase A2
Arachidonic Acid
Cyclo-oxygenase
PGG2 & PGH2
Thromboxane synthase
Prostacyclin synthase
(Platelets)
(Vascular endothelium)
TXA2
PGI2
Aggregation
Anti-aggregation
Contraction
Relaxation
Platelet interactions with agonists and antagonists of platelet aggregation, the vessel wall, other
platelets, and adhesive macromolecules. Agents in parentheses prevent the formation or inhibit
the function of the adjacent agonists of platelet aggregation. ADP = adenosine diphosphate, VWF
= von Willebrand factor, cAMP = cyclic adenosine monophosphate, GP = glycoprotein.
 3. Release or secretion:
Platelets contain alpha and dense granules
 Dense granules: containing ADP or ATP, calcium,
and serotonin
 α-granules: containing platelet factor 4, PDGF,
fibronectin, B-thromboglobulin, vWF, fibrinogen, and
coagulation factors V and XIII
Schematic drawing of the
platelet (top figure), showing its
alpha and dense granules and
canalicular system. The bottom
figure illustrates the platelet's
major functions, including
secretion of stored products,
as well as its attachment, via
specific surface glycoproteins
(GP), to denuded epithelium
(bottom) and other platelets
(left).
VWF: von Willebrand factor;
TSP: thrombospondin; PF4:
platelet factor 4; PDGF:
platelet derived growth factor;
-TG: beta thromboglobulin;
ADP: adenosine diphosphate;
ATP: adenosine triphosphate.
A schematic representation of selected platelet responses to activation and the congenital disorders of platelet function. AC =
adenylyl cyclase; BSS = Bernard–Soulier syndrome; CO = cyclooxygenase; DG = diacylglycerol; G = GTP-binding protein; IP3 =
inositol trisphosphate; MLC = myosin light chain; MLCK = myosin light chain kinase; P2Y1, P2Y12 = G-protein-coupled ADP
receptors; PAF = platelet activating factor; PGG2/PGH2 = prostaglandin arachidonic pathway intermediates; PIP2 =
phosphatidylinositol bisphosphate; PKC = protein kinase C; PLA2 = phospholipase A2; TK = tyrosine kinase; PLC = phospholipase
C; TS = thromboxane synthase; TxA2 = thromboxane A2; vWD = von Willebrand disease; vWF = von Willebrand factor. The
Roman numerals in the circles represent coagulation factors and yellow Ps indicate phosphorylation. (Modified with permission
from Rao AK: Congenital disorders of platelet function: disorders of signal transduction and secretion. Am J Med Sci 1998;
316:69-76.)
 4. Contraction
Clot retraction (血块回缩)
 5. Adsorption
Clotting factors: I, V, XI, XIII
Production of Platelets (Thrombocytes)
 Formation
 Large multinucleated cells that pushes against the wall
of the capillary
 Cytoplasmic extensions stick through and separate
Thrombopoietin
 Thrombopoietin (leukemia virus oncogene
ligand, megakaryocyte growth and
development factor), is a glycoprotein
hormone produced mainly by the liver and
the kidney that regulates the production of
platelets by the bone marrow
 It stimulates the production and
differentiation of megakaryocytes, the bone
marrow cells that fragment into large
numbers of platelets
Hemostasis（止血）
The arrest of bleeding following injury and the
result of 3 interacting, overlapping mechanisms:
 Vascular spasm（血管收缩）
 Formation of a platelet plug（血小板血栓形成）
 Blood coagulation (clotting)（血液凝固）
Bleeding time (出血时间)：<9 min
Role of vascular endothelium in
hemostasis
o Vasoconstriction: reduced blood flow facilitates
contact activation of platelets and coagulation factors
o Exposure of sub-endothelial basement membrane
and collagen
o Release of tissue thromboplastins (组织因子)
o Synthesis of basement membrane components,
tissue factor (组织因子), vWF, plasminogen activator
(纤溶酶原激活物), antithrombin III (抗凝血酶
III), thrombomodulin (血栓调节蛋白)
Signaling mediates responses to damage in a blood vessel:
adjacent endothelial cells are a source of signals that influence
platelet aggregation and alter blood flow and clot formation at the
affected site.
Role of platelets in hemostasis
 Release of vasoconstricting substances
 Formation of the "platelet plug"
 Promotion of blood clotting
 Clot retraction
 Blood
coagulation
Clotting factors
Clotting factor
Synonyms
I
II
III
IV
V
VII
VIII
IX
X
XI
XII
XIII
fibrinogen纤维蛋白原
prothrombin凝血酶原
tissue thromboplastin组织因子
Ca2+
proaccelerin前加速素易变因子
proconvertin前转变素稳定因子
antihemophilic factor抗血友病因子
plasma thromboplastin component血浆凝血活酶
Stuart-Prower factor
plasma thromboplastin antecedent血浆凝血活酶前质
contact factor接触因子
fibrin-stabilizing factor纤维蛋白稳定因子
The liver plays a critical role
in producing and
modifying blood-borne
proteins, including those
used in the clotting
pathway.
Moreover, bile salts from the
liver facilitate the absorption
of lipids in the diet, including
vitamin K,
which is required for the
synthesis of prothrombin.
Exploration of the details of the clotting pathway has
yielded detailed information about the sequence,
only a portion of which is represented here.
Note thrombin’s influence in three different directions.
Knowledge that
thrombin plays a
central role in clotting
has generated detailed
studies of the possible
pathways resulting in
its formation:
the extrinsic pathway is
the more important of
the two under most
circumstances.
Coagulation cascade
3 processes
2 pathways
Tissue factor pathway (extrinsic)
 Following damage to the blood vessel, endothelium Tissue Factor (TF)






is released, forming a complex with FVII and in so doing, activating it
(TF-FVIIa).
TF-FVIIa activates FIX and FX.
FVII is itself activated by thrombin, FXIa, plasmin, FXII and FXa.
The activation of FXa by TF-FVIIa is almost immediately inhibited by
tissue factor pathway inhibitor (TFPI).
FXa and its co-factor FVa form the prothrombinase complex, which
activates prothrombin to thrombin.
Thrombin then activates other components of the coagulation cascade,
including FV and FVIII (which activates FXI, which, in turn, activates
FIX), and activates and releases FVIII from being bound to vWF.
FVIIIa is the co-factor of FIXa, and together they form the "tenase"
complex, which activates FX; and so the cycle continues. ("Tenase" is a
contraction of "ten" and the suffix "-ase" used for enzymes.)
Contact activation pathway (intrinsic)
 The contact activation pathway begins with formation of the
primary complex on collagen by high-molecular-weight kininogen
(HMWK), prekallikrein, and FXII (Hageman factor). Prekallikrein
is converted to kallikrein and FXII becomes FXIIa.
 FXIIa converts FXI into FXIa.
 Factor XIa activates FIX, which with its co-factor FVIIIa form the
tenase complex, which activates FX to FXa.
 The minor role that the contact activation pathway has in
initiating clot formation can be illustrated by the fact that patients
with severe deficiencies of FXII, HMWK, and prekallikrein do not
have a bleeding disorder.
Final common pathway
 Thrombin has a large array of functions
 Its primary role is the conversion of fibrinogen to fibrin, the building block of a
hemostatic plug.
 In addition, it activates Factors VIII and V and their inhibitor protein C (in the
presence of thrombomodulin), and it activates Factor XIII, which forms
covalent bonds that crosslink the fibrin polymers that form from activated
monomers.
 Following activation by the contact factor or tissue factor
pathways, the coagulation cascade is maintained in a
prothrombotic state by the continued activation of FVIII and FIX
to form the tenase complex, until it is down-regulated by the
anticoagulant pathways.
Structure of
Fibrinogen
Fibrin
Polymerization
A deficiency of a clotting factor can lead to
uncontrolled bleeding.
Vitamin K is a cofactor needed for the synthesis of
factors II, VII, IX, & X in the liver. So a deficiency of
Vitamin K predisposes to bleeding.
Hemophilia
&
Bolshevik
Revolution
Rasputin
http://en.wikipedia.org/wiki/Grigori_Rasputin
http://www.sciencecases.org/hemo/hemo.asp
Serum （血清）
serum = plasma – fibrinogen and
some of the other clotting factors
+ substances released by vascular
endothelial cells and
platelets
Clotting time (凝血时间)：4-12 min
 Which of the following statements is correct?
A Damaged tissue releases a substance called tissue fibrinogen, which is mainly
composed of phospholipids
B Damage to the vessel wall initiates what is called the intrinsic pathway
C The activation of protein coagulation factor plus the release of platelet
thromboplastin eventually leads directly to the formation of thrombin
D The actual blood clotting is caused by a conversion of the plasma protein
prothrombin into another protein thrombin, which is the enzyme that causes
the polymerization of the plasma fibrinogen molecules into fibrin threads that
lead to blood clotting
E Damage to platelets causes the release of platelet thromboplastin, which has
an effect similar to tissue prothrombin
Anticoagulants（抗凝物质）
 Serine Protease Inhibitor
 Antithrombin III（抗凝血酶III）:
inhibiting all serine
proteases of the blood coagulation system, including:
 thrombin
 factor IXa, Xa, XIa, XIIa
 Protein C system（蛋白C系统）
 Protein C, thrombomodulin, Protein S…
In an uninjured vessel,
thrombin bound to
thrombomodulin activates
protein C, which blocks the
clotting response.
 Tissue factor pathway inhibitor (TFPI)（组织因子途径抑
制物）
 Heparin（肝素）
 A polysaccharide produced by the tissue mast cells and the
basophils of circulating blood
 Interfering primarily with the action of thrombin after
combining with antithrombin III
Fibrinolysis（纤维蛋白溶解）
o 2 processes
o Activation of plasminogen
o Degradation of fibrin
o 4 components of plasma fibrinolysis system
o Plasminogen（纤维蛋白溶解酶原）
o Plasmin（纤维蛋白溶解酶）
o Plasminogen activator
o Plasminogen inhibitor
Following tissue repair, fibrin clots are dissolved in a
process mediated by plasmin; synthetic plasminogen
activators can be used immediately after a stroke or
heart attack to help dissolve clots and restore blood flow.
o 2 pathways of plasminogen activation
Fibrin Degradation Products (FDP)
o Extrinsic Plasminogen activator
Tissue-type plasminogen activator (tPA)
Urokinase
o Plasminogen inhibitor
Plasminogen activator inhibitor type-1 (PAI-1)
2-antiplasmin
Antithrombin III
 Which of the following substances enzymatically causes the
polymerization of plasma fibrinogen?
A
B
C
D
E
Thromboplastin
Prothrombin
Prothrombin Activator
Thrombin
Phospholipids
 Which of the following cases would result in a fatal
transfusion reaction?
A Donor group A, Host group A
B Donor group AB negative, Host group AB and Rh positive
C Donor Rh negative, host Rh positive, medical history is
negative for prior transfusions
D Donor group AB, Host group 0
E Donor group 0, Host group AB
CASE
A woman brings her 13-year-old son to the pediatrician's office. The boy's
problems go back to the neonatal period, when he bled unduly after circumcision.
When his deciduous (baby) teeth first erupted, he bit his lower lip, and the wound
oozed for 2 days. As he began to crawl and walk, bruises appeared on his arms and
legs. Occasionally he would sustain a nosebleed without having had an obvious
injury. By the time he was 3 years of age, his parents became aware that
occasionally he would have painful swelling of a joint—a knee, shoulder, wrist, or
ankle—but his fingers and toes seemed spared. The joint swelling would be
accompanied by exquisite tenderness; the swelling would subside in 2 to 3 days.
The patient's mother states that when her son was a baby, she had noted what
appeared to be blood in his stool, and the boy tells the pediatrician that twice his
urine appeared red for 1 or 2 days.
Anxiously the patient's mother relates that her brother and her maternal uncle
both had similar problems and were thought to be "bleeders." There is no further
family history of bleeding, and there is no parental consanguinity (i.e., the patient's
parents are not blood relatives). Examination of this boy reveals the presence of
ecchymoses (bruises) and the inability to fully flex or extend his elbows.
A panel of four tests is ordered, with instructions to extend testing as appropriate.
The four tests are a (1) platelet count, (2) prothrombin time, (3) partial
thromboplastin time, and (4) bleeding time.
The patient's platelet count was found to be 260,000/ L (normal, 150,000 to
300,000/ L). This finding appears to rule out a paucity or excess of platelets as the
cause of bleeding.
1. What is the role of platelets in hemostasis (the control of bleeding)?
2. What purpose is served by drawing blood into a solution of sodium citrate? What is the purpose of adding a
solution of calcium chloride? Does the prothrombin time measure the intrinsic or extrinsic pathway of
coagulation?
3. What mechanisms might cause the prothrombin time to be abnormally long?
4. With the given data, can you guess in general the site of the clotting abnormality in this patient?
5. Which clotting factors participate in the early steps of the intrinsic pathway of thrombin formation?
6. In reference to the patient's history, is there a discernible pattern in the way the patient's disorder might be
inherited?
7. As in the case of the prothrombin time, what mechanisms might be responsible for a long partial thromboplastin
time?
8. Diagnosis is made easier because deficiency of certain clotting factors either causes no symptoms or is
associated only with much milder bleeding problems than the patient manifests. Which disorders can be set
aside on this basis?
9. It is possible that the patient is functionally deficient in one of two clotting factors? Which are these? Can you
propose a way to determine which deficiency is present?
10. Had the bleeding time been long, what diagnoses must be considered?
11. How does the bleeding time help to further delineate the diagnosis?
12. The patient's mother then added that her son's former physician had made a diagnosis of classic hemophilia.
She asks, "What are the odds that his sister, now 17, is a carrier?"
Thank you for your attention!