BLEEDING DISORDERS AND SURGICAL HAEMATOLOGY
INTRODUCTION
Bleeding disorders refer to a wide range of medical problems that lead to poor blood clotting and
prolonged bleeding. It is of prime importance for a surgeon to be able to identify his patient’s
coagulation profile in the elective as well as in the emergent circumstances. The seminar will focus
on some of the most commonly encountered bleeding disorders that affect peri-operative care.
PHYSIOLOGY OF COAGULATION (Haemostasis) 15,16
Clotting is the process by which haemostasis is achieved. Haemostasis can be divided into 2 stages,
primary and secondary. Primary haemostasis includes platelet and vascular response to vessel injury;
secondary haemostasis involves coagulation factors in response to such an injury. Together,
platelets, vessels, and coagulation factors combine to stop bleeding and allow for vessel repair
through formation of a stable fibrin-platelet plug at the site of injury.
• Vasoconstriction helps in reducing blood flow
• Platelets adhere to the vascular endothelium
• Platelet activation and aggregation along with enzymatic reactions produce fibrin
Mechanism of haemostasis by vasoconstriction
Following injury, via sympathetic, local and humoral factors, the blood vessel constricts. The prime
mediator of this are humoral factors which are released by activated platelets, namely ADP,
epinephrine, norepinephrine, kinins and thromboxanes. The vascular endothelium contains a layer of
smooth muscle cells that contract in response to the above substances. Fibrin degradation products
also affect vasoconstriction. The resultant decrease in the lumen size of the bleeding vessel
obviously reduces hemorrhage.
Mechanism of action of platelets in haemostasis 8
• Adhesion
Platelets adhere to the injured vascular endothelium when von Willebrand factor (vWf) binds to
the exposed collagen in the wall of the injured vessel (leads to release of Calcium ions and
platelet activation) and binding of vWf to platelet membrane receptor GP1b/IX.
• Activation
During activation the Calcium ion concentration in the cytoplasm almost doubles. The activation
causes a change in the morphology of the cell to a more spherical shape and hence increasing the
surface area. Actin also polymerises inside the cytoplasm and along with the increase in
cytoplasmic Calcium ion concentration, vWf and fibrinogen are released.
• Aggregation:
As depicted in diagram, once platelets are activated, the GP IIb/IIIa anchor becomes functional on
the cell membrane. Fibrinogen can bind 2 such molecules and hence bridges platelets and forms
aggregates.
1
, • Membrane phospholipids:
The phospholipid bilayer of the platelet membrane carries a negative charge enabling multiple
reactions of coagulation to occur. This negative charge is what binds calcium ions to the
membrane.
Coagulation Pathways: (Refer to Seminar by Dr. A. Saloojee, Sem. No. 7, 26/02/2011, UKZN
archives)
Risk Assessment for Bleeding Disorders 31
History: A thorough history is the single most significant and important diagnostic tool in the
establishment and severity of a bleeding diathesis. A meticulous history is essentially necessary in
two circumstances.
(a) When clinical finding or past medical history points to a disorder of homeostasis.
(b) In patients who do not show obvious homeostatic disorder but who are scheduled for major
surgery.
Clues to congenital disorders are:
(a) Excessive bleeding initiated common childhood trauma e.g. tooth extraction.
(b) History of bleeding disorder in family & when mode of inheritance can be determined, it may
suggest diagnosis
as well eg X-linked in hemophilia A & B. Autosomal inheritance with low factor VIII C Icvcl
suggests vWf
Clues to acquired disorders are:
(a) Patients giving history of tolerating stress to homeostatic system eg tooth extraction but
presenting with a
bleeding tendency in recent times
(b) Exposure to potentially causative factors and onset of bleeding episodes
Nature of bleeding: Sites of bleeding may suggest where in the coagulation process the defect may
be seen eg:
(i) Mucous membrane bleeding and petechiae are seen in platelet disorders.
(ii) Haemarthrosis is common in Hemophilia.
(iii) Soft tissue hematoma without petechiae, a mucous membrane bleeding suggests a defect in
1o haemostasis
2
INTRODUCTION
Bleeding disorders refer to a wide range of medical problems that lead to poor blood clotting and
prolonged bleeding. It is of prime importance for a surgeon to be able to identify his patient’s
coagulation profile in the elective as well as in the emergent circumstances. The seminar will focus
on some of the most commonly encountered bleeding disorders that affect peri-operative care.
PHYSIOLOGY OF COAGULATION (Haemostasis) 15,16
Clotting is the process by which haemostasis is achieved. Haemostasis can be divided into 2 stages,
primary and secondary. Primary haemostasis includes platelet and vascular response to vessel injury;
secondary haemostasis involves coagulation factors in response to such an injury. Together,
platelets, vessels, and coagulation factors combine to stop bleeding and allow for vessel repair
through formation of a stable fibrin-platelet plug at the site of injury.
• Vasoconstriction helps in reducing blood flow
• Platelets adhere to the vascular endothelium
• Platelet activation and aggregation along with enzymatic reactions produce fibrin
Mechanism of haemostasis by vasoconstriction
Following injury, via sympathetic, local and humoral factors, the blood vessel constricts. The prime
mediator of this are humoral factors which are released by activated platelets, namely ADP,
epinephrine, norepinephrine, kinins and thromboxanes. The vascular endothelium contains a layer of
smooth muscle cells that contract in response to the above substances. Fibrin degradation products
also affect vasoconstriction. The resultant decrease in the lumen size of the bleeding vessel
obviously reduces hemorrhage.
Mechanism of action of platelets in haemostasis 8
• Adhesion
Platelets adhere to the injured vascular endothelium when von Willebrand factor (vWf) binds to
the exposed collagen in the wall of the injured vessel (leads to release of Calcium ions and
platelet activation) and binding of vWf to platelet membrane receptor GP1b/IX.
• Activation
During activation the Calcium ion concentration in the cytoplasm almost doubles. The activation
causes a change in the morphology of the cell to a more spherical shape and hence increasing the
surface area. Actin also polymerises inside the cytoplasm and along with the increase in
cytoplasmic Calcium ion concentration, vWf and fibrinogen are released.
• Aggregation:
As depicted in diagram, once platelets are activated, the GP IIb/IIIa anchor becomes functional on
the cell membrane. Fibrinogen can bind 2 such molecules and hence bridges platelets and forms
aggregates.
1
, • Membrane phospholipids:
The phospholipid bilayer of the platelet membrane carries a negative charge enabling multiple
reactions of coagulation to occur. This negative charge is what binds calcium ions to the
membrane.
Coagulation Pathways: (Refer to Seminar by Dr. A. Saloojee, Sem. No. 7, 26/02/2011, UKZN
archives)
Risk Assessment for Bleeding Disorders 31
History: A thorough history is the single most significant and important diagnostic tool in the
establishment and severity of a bleeding diathesis. A meticulous history is essentially necessary in
two circumstances.
(a) When clinical finding or past medical history points to a disorder of homeostasis.
(b) In patients who do not show obvious homeostatic disorder but who are scheduled for major
surgery.
Clues to congenital disorders are:
(a) Excessive bleeding initiated common childhood trauma e.g. tooth extraction.
(b) History of bleeding disorder in family & when mode of inheritance can be determined, it may
suggest diagnosis
as well eg X-linked in hemophilia A & B. Autosomal inheritance with low factor VIII C Icvcl
suggests vWf
Clues to acquired disorders are:
(a) Patients giving history of tolerating stress to homeostatic system eg tooth extraction but
presenting with a
bleeding tendency in recent times
(b) Exposure to potentially causative factors and onset of bleeding episodes
Nature of bleeding: Sites of bleeding may suggest where in the coagulation process the defect may
be seen eg:
(i) Mucous membrane bleeding and petechiae are seen in platelet disorders.
(ii) Haemarthrosis is common in Hemophilia.
(iii) Soft tissue hematoma without petechiae, a mucous membrane bleeding suggests a defect in
1o haemostasis
2
