UKRAINIAN MINISTRY OF PUBLIC HEALTH

VINNYTSYA NATIONAL PYROGOV MEMORIAL MEDICAL UNIVERSITY

«approved»
At the methodological meeting of the
internal medicine propedeutics department
Chief of the department
____________ prof. Mostovoy Y.M.
«______»_______________ 2017

Guidelines
For third-year students of the medical department

Subgect Propedeutics of the internal medicine

Modul № 2
Enclosure module № 7
Topic Hemorrhagic syndrome and disorders of coagulation.
Disseminated intravascular coagulation syndrome
Course 3
Faculty Medical № 1

Methodical recommendations are made in accordance with educationally-qualifying descriptions

and educationally-professional programs of preparation of the specialists ratified by order MES
of Ukraine of 16.05 2003 № 239 and experimentally - curriculum, that is developed on principles
of the European credit-transfer system (ECTS) and Ukraine ratified by the order of MPH of
Ukraine of 31.01.2005 № 52.

Vinnytsya- 2017
 1. Importance of the topic
Hemorrhagic syndrome usually is developed due to disorders of coagulation system. It
may accompany a lot of different internal diseases and frequently is developed after
surgical and obstetrical interventions. Underestimation of possible risk of coagulation
disorders and clinical symptoms and signs of the syndromes result in life-threatening
conditions which are treated very difficulty. Knowledge about manifestations of the
hemorrhagic syndrome and understanding mechanisms of development of the clotting
disorders is very important for physicians of every specialty.

2. Concrete aims:
─ To study types of hemorrhagic diathesis
─ To study laboratory tests of the hemostatic system
─ To study main symptoms and signs of hemophilia
─ To study main symptoms and signs of thrombocytopenia
─ To study main symptoms and signs of vascular wall disorders

3. Basic training level

Previous subject Obtained skill

Normal anatomy Anatomy of the hematopoietic system
Normal physiology Principles of blood coagulation
Histology Ontogenesis and histological structure of the bone marrow and
hematopoietic system

4. Task for self-depending preparation to practical training

4.1. List of the main terms that should know student preparing practical training

Term Term
hematoma petechiae
ecchymoses telangiectasia
purpura bleeding time
partial thromboplastin time prothrombin time

4.2. Theoretical questions:

1. What types of hemorrhagic diathesis do you know?
2. What laboratory tests are used for assessment of the primary hemostasis?
3. How is the plasma coagulation function assessed?
4. Hemophilia, definition, classification.
5. Clinical presentation of the hemophilia.
6. Clinical presentation of the thrombocytopena
7. Clinical presentation of the Henoch-Schonlein purpura

4.3. Practical task that should be performed during practical training

1. To assess types of hemorrhagic diathesis
2. To assess results of coagulation system tests

5. Topic content
Normal mechanism of hemostasis:
Vasoconstriction following by a vascular injury
Primary hemostasis – formation of the platelet plug at the site on injury
Secondary hemostasis – reaction of the plasma coagulation system that results in fibrin formation
Types of hemorrhagic diathesis
1. Hematomas are large painful, deep and palpable subcutaneous, intramuscular collections of
blood. Bleeding into body cavities, the retroperitoneum, or joints is a common manifestation
of plasma coagulation defects. Repeated joint bleeding may cause synovial thickening,
chronic inflammation, and fluid collections and may erode articular cartilage and lead to
chronic joint deformity and limited mobility. Joint deformities are particularly common in
patients with deficiencies of factors VIII and IX, the two sex-linked coagulation disorders
referred to as the hemophilias. For unclear reasons, hemarthroses are much less common in
patients with other plasma coagulation defects. Blood collections in various body cavities or
soft tissues can cause secondary necrosis of tissues or nerve compression. Retroperitoneal
hematomas can cause femoral nerve compression, and large collections of poorly coagulated
blood in soft tissues occasionally mimic malignant growths—the pseudotumor syndrome.
Two of the most life-threatening sites of bleeding are in the oropharynx, where bleeding can
compromise the airway, and in the central nervous system. Intracerebral hemorrhage is one
of the leading causes of death in patients with severe coagulation disorders.
2. Collections of blood in the skin are called purpura and may be subdivided on the basis of the
site of bleeding in the skin. Small pinpoint hemorrhages into the dermis due to the leakage of
red cells through capillaries are called petechiae and are characteristic of platelet disorders—
in particular, severe thrombocytopenia.
3. Larger subcutaneous collections of blood due to leakage of blood from small arterioles and
venules are called ecchymoses (common bruises). They are also common in patients with
platelet defects and result from minor trauma.
4. Dilated capillaries, or telangiectasia, may cause bleeding without any hemostatic defect. In
addition, the loss of connective tissue support for capillaries and small veins that
accompanies aging increases the fragility of superficial vessels, such as those on the dorsum
of the hand, leading to extravasation of blood into subcutaneous tissue—senile purpura.
Laboratory tests of the hemostatic system
The most important screening tests of the primary hemostatic system are
1)a bleeding time (a sensitive measure of platelet function),
2) a platelet count.
The normal platelet count is 150 to 450*109/L of blood. As long as the count is >100*109/L,
patients are usually asymptomatic and the bleeding time remains normal. Platelet counts of 50 to
100*109/L cause mild prolongation of the bleeding time; bleeding occurs only from severe
trauma or other stress. Patients with platelet counts <50*109/L have easy bruising, manifested are
characteristic of platelet disorders—in particular, severe thrombocytopenia. Patients with a
platelet count <20*109/L have an appreciable incidence of spontaneous bleeding, usually have
petechiae and may have intracranial or other spontaneous internal bleeding.
Patients with qualitative platelet abnormalities have a normal platelet count and a prolonged
bleeding time. The bleeding time is ascertained by making a small, superficial skin incision and
timing the duration of blood flow from the wounded area. With careful standardization, bleeding
time is a reliable and sensitive test of platelet function.
Any patient with a bleeding time >10 min has an increased risk of bleeding, but the risk does not
become great until the bleeding time is >15 or 20 min.
Plasma coagulation function is readily assessed with
1. the partial thromboplastin time (PTT),
2. prothrombin time (PT),
3. thrombin time (TT), and
4. quantitative fibrinogen determination.
The PTT screens the intrinsic limb of the coagulation system and tests for the adequacy of
factors XII, HMWK, PK, XI, IX, and VIII. The PT screens the extrinsic or tissue factor–
dependent pathway. Both tests also evaluate the common coagulation pathway involving all the
reactions that occur after the activation of factor X. Prolongation of the PT and PTT that does not
resolve after the addition of normal plasma suggests a coagulation inhibitor. A specific test for
the conversion of fibrinogen to fibrin is needed when both the PTT and PT are prolonged—either
a TT or a clottable fibrinogen level can be employed. When abnormalities are noted in any of the
screening tests, more specific coagulation factor assays can be ordered to determine the nature of
the defect.
HEMOPHILIA
A hereditary bleeding disorder, hemophilia results from the deficiency of specific clotting factors.
Hemophilia A (classic hemophilia), which affects more than 80% of all hemophiliacs, results from
a deficiency of factor VIII; hemophilia В (Christmas disease), which affects 15% of hemophiliacs,
results from a deficiency of factor IX.
The severity and prognosis of bleeding disorders vary with the degree of deficiency and the site
of bleeding. The overall prognosis is best in mild hemophilia, which doesn't cause spontaneous
bleeding and joint deformities.
Advances in treatment have greatly improved the prognosis, and many hemophiliacs live
normal life spans. Surgical procedures can be done safely at special treatment centers for hemo-
philiacs under the guidance of a hematologist.
Causes
Hemophilia A and hemophilia В are inherited as X-linked recessive traits. This means that female
carriers have a 50% chance of transmitting the gene to each daughter, who would then be a carrier,
and a 50% chance of transmitting the gene to each son, who would be born with hemophilia.
Incidence
Hemophilia is the most common X-linked genetic disease, occurring in about 1.25 in 10,000
live male births. Hemophilia A is five times more common than hemophilia B. Hemophilia
causes abnormal bleeding because of a specific clotting factor malfunction. After a person with
hemophilia forms a platelet plug at a bleeding site, clotting factor deficiency impairs the capacity
to form a stable fibrin clot.
Signs and symptoms
Hemophilia produces abnormal bleeding, which may be mild, moderate, or severe, depending on
the degree of factor deficiency.
Mild hemophilia
The mild form of hemophilia frequently goes undiagnosed until adulthood because the patient with
a mild deficiency doesn't bleed spontaneously or after minor trauma but has prolonged bleeding if
challenged by major trauma or surgery. Postoperative bleeding continues as slow ooze or ceases
and starts again up to 8 days after surgery.
Moderate and severe hemophilia
Moderate hemophilia causes symptoms similar to those of severe hemophilia but produces only
occasional spontaneous bleeding episodes.
Severe hemophilia causes spontaneous bleeding. The first sign of severe hemophilia usually is
excessive bleeding after circumcision. Later, spontaneous bleeding or severe bleeding after minor
trauma may produce large subcutaneous and deep intramuscular hematomas.
Bleeding into joints and muscles causes pain, swelling, extreme tendeness and, possibly,
permanent deformity. Bleeding near peripheral nerves may cause peripheral neuropathies, pain,
paresthesia, and muscle atrophy.
If bleeding impairs blood flow through a major vessel, it can cause ischemia and gangrene.
Pharyngeal, lingual, intracardial, intracerebral, and intracranial bleeding may lead to shock and
death.
Diagnosis
A history of prolonged bleeding after trauma or surgery (including dental extractions) or of
episodes of spontaneous bleeding into muscles or joints usually indicates some defect in the
hemostatic mechanism.
 Specific coagulation factor assays can diagnose the type and severity of hemophilia. A positive
family history can also help diagnose hemophilia, but 20% of all cases have no family history.
Characteristic findings in hemophilia A include:
• factor VIII assay 0% to 30% of normal
• prolonged activated partial thromboplastin time (APTT)
• normal platelet count and function, bleeding time, and prothrombin time.
Characteristics of hemophilia В include:
• deficient factor IX-C
• baseline coagulation results similar to those in hemophilia A, with normal factor VIII.
In hemophilia A or hemophilia B, the degree of factor deficiency determines severity:
 mild hemophilia—factor levels 5% to 40% of normal
 moderate hemophilia—factor levels 1% to 5% of normal
 severe hemophilia — factor levels < 1% of normal.
THROMBOCYTOPENIA
The most common cause of hemorrhagic disorders, thrombocytopenia is characterized by
deficiency of circulating platelets. Because platelets play a vital role in coagulation, this
disease poses a serious threat to hemostasis.
Causes
Thrombocytopenia may be congenital or acquired; the acquired form is more common. In either
case, it usually results from the following:
• decreased or defective production of platelets in the marrow (such as occurs in leukemia,
aplastic anemia, or toxicity with certain drugs)
• increased destruction outside the marrow caused by an underlying disorder (such as cirrhosis of
the liver, disseminated intravascular coagulation, or severe infection)
• less commonly, sequestration (hypersplenism, hypothermia) or platelet loss.
Acquired thrombocytopenia may result from certain drugs, such as non-steroidal anti-
inflammatory agents, sulfonamides, histamine blockers, alkylating agents, or antibiotic
chemotherapeutic agents.
An idiopathic form of thrombocytopenia commonly occurs in children. A transient form may
follow viral infections (Epstein-Barr or infectious mononucleosis).
Signs and symptoms
Most adults present with a more indolent form of thrombocytopenia that may persist for many
years and is referred to as chronic idiopatic trombocytopenic purpura. Women age 20 to 40 are
afflicted most commonly and outnumber men by a ratio of 3:1. They may present with an abrupt
fall in platelet count and bleeding into any mucous membrane. More often they have a prior
history of easy bruising (petechiae or ecchymoses) or menometrorrhagia. Nearly all patients are
otherwise asymptomatic, although some may complain of malaise, fatigue, and general weakness.
Splenomegaly is usually revealing at palpation of the abdomen.
In adults, large blood-filled. bullae characteristically appear in the mouth. In severe
thrombocytopenia, hemorrhage may lead to tachycardia, shortness of breath, loss of consciousness,
and death.
Diagnosis
To diagnose thrombocytopenia, obtain a patient history (especially a drug history), a physical
examination, and the following laboratory tests:
• Coagulation tests reveal a decreased platelet count (in adults, < 100,000/mcl), prolonged bleeding
time, and normal prothrombin time and partial thromboplastin time.
• If increased destruction of platelets is causing thrombocytopenia, bone marrow studies will reveal a
greater number of megakaryocytes (platelet precursors) and shortened platelet survival (several
hours or days rather than the usual 7 to 10 days).
VESSEL WALL DISORDERS
Bleeding from vascular disorders (nonthrombocytopenic purpura) is usually mild and confined
to the skin and mucous membranes. The pathogenesis of bleeding is poorly defined in many of
the syndromes, and classic tests of hemostasis, including the bleeding time and tests of platelet
function, are usually normal. Vascular purpura arises from damage to capillary endothelium,
abnormalities in the vascular subendothelial matrix or extravascular connective tissues that
support blood vessels, or from the formation of abnormal blood vessels. Several idiopathic
disorders involve the vessel wall and can cause more severe bleeding and organ dysfunction.
HENOCH-SCHONLEIN PURPURA
Henoch-Schonlein, or anaphylactoid, purpura is a distinct, self-limited type of vasculitis
that occurs in children and young adults. Patients have an acute inflammatory reaction in
capillaries, mesangial tissues, and small arterioles that leads to increased vascular permeability,
exudation, and hemorrhage. Vessel lesions contain IgA and complement components. The
syndrome may be preceded by an upper respiratory infection or streptococcal pharyngitis or be
associated with food or drug allergies. Patients develop a purpuric or urticarial rash on the
extensor surfaces of the arms and legs and on the buttocks (purpura simplex) as well as
polyarthralgias or arthritis (purpura rheumatic), colicky abdominal pain (purpura abdominalis),
and hematuria from focal glomerulonephritis (purpura renalis), or cerebral hemorrhage (purpura
cerebralis). Despite the hemorrhagic features, all coagulation tests are normal. A small number
of patients may develop fatal acute renal failure, and 5 to 10% develop chronic nephritis.

6.Material for self-control

Test for self-control

1. Hemarthrosis is characterized by:

A. Idiopathic thrombocytopenic purpura
B. Hemophilia*
C. Hemorrhagic vasculitis
D. Thrombocytopathy
E. Osler-Weber-Rendu Disease
2. Another name for idiopathic thrombocytopenic purpura is a:
A. Kahler's disease
B. Henoch-Schonlein purpura
C. Vaquez disease
D. Werlhof`s disease*
E. Cushing`s disease
3. Which pathology prolongs bleeding time according to Duke?
A. Hemophilia
B. Thrombocytopenic purpura*
C. Hemorrhagic vasculitis
D. Iron deficiency anemia
E. Hemolytic anemia
4. Hemophilia is related to:
A. Thrombocytopenia
B. Thrombocytopathy
C. Coagulopathy*
D. Amyloid-associated hemorrhagic diathesis
E. Vasopathy
5. "Leopard skin" is typical for:
A. Hemophilia
B. Hemorrhagic vasculitis
C. Thrombocytopenic purpura*
D. Iron deficiency anemia
E. B12-deficient anemia
6. Kidneys of patients with hemorrhagic vasculitis are affected in the form of:
A. Glomerulonephritis*
B. Pyelonephritis
C. Amyloidosis of the kidneys
D. Polycystic kidneys
E. Urolithiasis
7. Bleeding in the form of hematoma formation is characteristic for:
A. Idiopathic thrombocytopenic purpura
B. Thrombocytopathy
C. Hemophilia*
D. Hemorrhagic vasculitis
E. Osler-Weber-Rendu Disease
8. The basis for failure of organs` functioning in patients with DIC syndrome is:
A. Total spasm of arteries
B. Total paresis of arterioles
C. Systemic inflammation
D. Toxic lesion of organs
E. Microcirculation blockade*
9. The Werlhof’s disease is related to:
A. Thrombocytopenia*
B. Thrombocytopathy
C. Coagulopathy
D. Vasopathy
E. Amyloid-associated hemorrhagic diathesis
10. According to the current classification, Henoch–Schönlein purpura is:
A. Systemic vasculitis*
B. Oncologic disease
C. Leukemia
D. A kind of anemia
E. Systemic connective tissue disease
11. Hemorrhagic vasculitis is characterized by:
A. Extended bleeding time according to Duke
B. Severe thrombocytopenia
C. Extended blood coagulation time
D. Prevention of blood clot retraction
E. Positive Rumpel-Leede sign*
12. Hemophilia is related to:
A. Thrombocytopenia
B. Thrombocytopathy
C. Coagulopathy*
D. Amyloid-associated hemorrhagic diathesis
13. The vascular wall under hemorrhagic vasculitis is damaged as a result of:
A. Microbial inflammation in the vascular walls
B. Toxic impact of infection
C. Immune complex delay*
D. Absence of platelet trophic effect
E. Genetically determined vascular wall defect
14. Vascular-platelet hemostasis study method is:
A. Rumpel-Leede sampling
B. Duke's bleeding time, Ivy test
C. Platelets counting and aggregation study
D. Blood clot retraction
E. All above listed *
15. Coagulation hemostasis study method is:
A. Blood coagulation time
B. Plasma recalcification time
C. Prothrombin time/index
D. Thrombin time
E. All above listed *
16. Coagulation hemostasis study method is:
A. Activated partial thromboplastin time (APTT) *
B. Duke's bleeding time, Ivy test
C. Blood clot retraction
D. Platelet count
E. Rumpel-Leede sampling
17. Extended blood coagulation may indicate:
A. Insufficient factors of internal coagulation mechanism
B. Prothrombin deficiency
C. Fibrinogen deficiency
D. Presence of blood coagulation inhibitors, for example heparin
E. All above listed *
18. DIC syndrome is characterized by:
A. Intensive activation of the coagulation system
B. Generalized intravascular blood clotting with tissue circulation blockage
C. Coagulopathy associated with bleeding
D. Severe circulatory disorders, severe endogenous intoxication
E. All above listed*
19. Normal clot retraction is:
A. 5-10 min
B. 2-4 min
S. 30-40%
D. 40-95% *
E. 100%
20. DIC syndrome causes are:
A. Intensive and traumatic resuscitation
B. Massive blood transfusion
S. Burns
D. Massive bleeding
E. All above listed *

Situation tasks
1. Patient 34-years-old female came to the hospital with general weakness, epistaxis,
gum bleeding, prolonged menstrual bleeding, and rush on the legs. She was sick
last 2 years. Objective exam: petechial rush on the legs, ecchymosis on the trunk.
Data of the heart and lungs auscultation in a norm. Liver and spleen is not
palpable. Full blood test: Er. – 3.0*1012/L, Hb – 100 g/L, CI – 1.0, Leuc. –
7.8*109/L, eos – 3%, stab – 2%, seg – 63%, lym- 28%, mon – 4%, trom –
20.0*109/L, ESR – 12 mm/Hour.
1. What is possible disease?
2. What should the laboratory tests be prescribed?
3. What may be found in the bone marrow tests?
2. Patient 20-years-old male was hospitalized with hemarthrosis to the left knee joint
due to injury. He was sick from the first days of life. During childhood he had
injury of the right knee joint. His grand-father suffered from hemophilia A.
Patient skin and mucous membrane is pale. The left knee is enlarged without
 motions. The right knee joint is deformed, motions are limited, and muscles of legs
are atrophied. Auscultation data: the first heard sound is weakened over the apex,
systolic murmur over all points. Ps 100 bpm, soft, BP – 100/60 mm Hg. Full blood
test: Er. – 3.3*1012/L, Hb – 95 g/L, CI – 0.85, Ret. – 0.8‰, Leuc – 7.2*109/L, Trom.
- 280*109/L, ESR – 22 mm/Hour. Blood coagulation by Burger: start – 6 min, stop
– 16 min.
1. What are the changes in the full blood test?
2. What disease is characterized with these laboratory and clinical data?
3. What do additional laboratory tests help you confirm the disease?
Control questions:
1. What types of hemorrhagic diathesis do you know?
2. What laboratory tests are used for assessment of the primary hemostasis?
3. How is the plasma coagulation function assessed?
4. Hemophilia, definition, classification.
5. Clinical presentation of the hemophilia.
6. Clinical presentation of the thrombocytopena
7. Clinical presentation of the Henoch-Schonlein purpura
Practical task that should be performed during practical training
1. To assess types of hemorrhagic diathesis
2. To assess results of coagulation system tests

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Associate professor, MScD A.V. Demchuk

Associate professor M.V. Ovcharuk