This document discusses disorders of hemostasis, including excessive bleeding disorders and hypercoagulability states. It describes tests used to evaluate hemostasis such as prothrombin time, partial thromboplastin time, and platelet counts. Vascular disorders that can cause bleeding are discussed as well as inherited and acquired bleeding disorders involving platelets or coagulation factors. Specific disorders covered include hemophilia A, hemophilia B, von Willebrand disease, disseminated intravascular coagulation, and thrombocytopenia. Causes and complications of various bleeding and thrombotic disorders are summarized.

1. Associate Profes
Arsenteva
DISORDERS OF HEMOSTASIS

5. Thrombocytes
• potentiate the vascular spasm via vasoconstrictor
factors (TxA2, serotonin)
• contribute to the primary haemostasis via the
platelet plug formation
• participate in the secondary haemostasis via the
release of platelet membrane phospholipids

9. Excessive bleeding
• increased fragility of vessels
• platelet deficiency or dysfunction
• derangement of coagulation, alone or in
combination

10. Tests of Hemostasis
• Prothrombin time (PT). This test assesses the extrinsic and
common coagulation pathways (he reference range is 9.5-
13.5 seconds);
• Partial thromboplastin time (PTT). This test assesses the
intrinsic and common clotting pathways.
• Platelet counts (From 150 × 103 to 300 × 103 platelets/μL)
• Tests of platelet function. Lower - “thrombocytopenia”,
higher – “thrombocythemia”.
• International normalized ratio (INR) (the reference range is
less than 1.3)

11. VASCULAR disorders
(vascular purpuras)
• do not usually cause serious bleeding problems
• small blood vessels are affected (capillaries and
arterioles)
• small visible hemorrhages (petechiae and purpura)
• the platelet count and the coagulation tests (PT,
aPTT) are usually normal
• bleeding time (BT) is prolonged.

12. Hereditary haemorrhagic telangiectasia
(Rendu-Osler-Weber syndrome)
• hereditary disorder of vascular malformation
transmitted as autosomal dominant disorder
• Pathogenesis: mutations of genes which codes for
endothelial proteins involved in hormones signal
transduction of the transforming growth factor β
superfamily (TGFβ), which are decreased.

13. Acquired vascular purpuras
• Purpura from vitamin C deficiency (scurvy)
• Senile purpura
• Steroid purpura
• Purpura due to infections
• Allergic vascular purpuras

14. Purpura from vitamin C
deficiency (scurvy)
• Swelling and bleeding of the
gums
• Disseminated petechiae
• Poor wound healing
• Hair and tooth loss
• Small bleeding around the hair
follicles (Corkscrew hair)
• Small bleeding under nails
• Dry, pale skin

15. Senile purpura
• Easy bruising in elderly
people due to dermal
tissues atrophy leads to
fragile vessel walls.
• Clinical features:
persistent dark purple
ecchymosis without
known trauma, mostly
located on the surfaces
of the hands and
forearms.

16. Steroid purpura
- Loss of perivascular supporting tissue because of
protein-wasting effects of high corticosteroid level
- Impaired collagen synthesis.

17. Purpura due to infections
• associated with septicemia or
viremia
• toxic damage to the vascular
walls:
• directly: toxins damage →
vasculitis
• indirectly: disseminated
intravascular coagulation (DIC)

18. Anaphylactoid purpura
(Schonlein-Henoch syndrome)
● extrarenal manifestations – triade: cutaneous rash, colicky
abdominal pain (due to focal hemorrhages in GI tract),
polyarthralgia (transient arthralgia of large joints)
● renal manifestations: acute glomerulonephritis & renal
failure

20. Thrombocytopenia
• Reduction in platelet number < 100.000/mm3
• Spontaneous bleeding does not become evident
until the count falls below 20.000/mm3
• Spontaneous bleeding associated with
thrombocytopenia most often involves small
vessels.
• The common sites: skin and the mucous
membranes of the gastrointestinal and
genitourinary tracts.

22. Idiopathic/Immune Thrombocytopenic Purpura
(ITP, Werlhof disease)

23. Idiopathic/Immune Thrombocytopenic
Purpura (ITP, Werlhof disease)
Clinical forms:
• 1. The acute form
• 2. The chronic form

24. Heparin-Induced Thrombocytopenia (HIT)

26. Hemolytic-Uremic Syndrome (HUS)

27. Thrombocytopathia
Altered platelet function + normal number of thrombocytes
Causes:
1. Inherited disorders of:
• a. Adhesion (von Willebrand disease and Bernard-Soulier
syndrome)
• b. Aggregation (Glanzmann thrombasthenia)
2. Acquired functional defects caused by:
• a. Drugs (aspirin and NSAIDs)
• b. Toxins (uremia)

30. Thrombocytopathias
• Disorders of adhesion (Bernard–Soulier syndrome -
autosomal recessive disorder): a defect in the glycoprotein
Ib, large platelets in periferal blood, bleeding time is
prolonged.
• Disorders of aggregation (Glanzmann thrombas-thenia -
autosomal recessive disorder): a defect in the platelet
glycoprotein IIb/IIIa complex (role of receptor for
fibrinogen): platelets cannot aggregate
• TREATMENT: Platelet transfusion

31. Thrombocytopathias
• Disorders of activation:
• hereditary intrinsic platelet disorders (decreased ADP in
the platelet granules decreased ADP in the platelet
granules, inability to generate TxA2 from arachidonic
acid, inability of platelets to aggregate in response to
TxA2)
• use of NSAIDs or aspirin (because of COX-1 inhibition)

32. Coagulation disorders
• A. Hereditary defects :
1. Von Willebrand disease
2. Hemophilia A – factor VIII deficiency
3. Hemophilia B – factor IX deficiency
• B. ACQUIRED coagulation disorders
1. Decreased synthesis of clotting factors:
• a) Liver diseases
• b) Vitamin K deficiency
2. Increased consumption of clotting factors:
• a) Disseminated intravascular coagulation (DIC)
von Willebrand disease (vWD)

34. HEMOPHILIA A - factor VIII deficiency
Clinical manifestations:
- Bruises and hematoma
- Bleeding into joints with pain and swelling
(hemarthrosis)
- Gastrointestinal and urinary tract hemorrhage
! Never purpura and petechiae (since primary
hemostasis is not affected)
- Positive diagnosis:
prolonged APTT
normal BT, PT, and platelet count
low factor VIII concentration
Treatment: recombinant factor VIII, sometimes
antifibrinolytics

35. Hemophilia A: mechanisms

36. HEMOPHILIA B, factor IX deficiency
(Christmas disease)
• The same clinical
manifestations as in
hemophilia A
• presents the same
screening test
abnormalities.
• Treatment:
recombinant factor IX.

37. Vitamin K deficiency
• Vitamin K is required for the carboxylation (activation)
of the clotting factors II (prothrombin), VII, IX, X.
• gamma-carboxyglutamic acid ↔ glutamic acid; no
activation of prothrombin to thrombin.
• Causes of vitamin K deficiency:
- decreased synthesis by intestinal bacteria
- impaired intestinal absorption (lack of bile salts)
- inhibition of activity in vitamin K antagonists over
dosage (oral anticoagulant drugs of coumar type)

38. Liver disease → coagulation defects
• Hepatocellular damage → decreased coagulation
factors synthesis
• Cholestasis → vitamin K malabsorption → decreased
activation of clotting factors
• Portal hypertension → splenomegaly and
hypersplenism → thrombocytopenia
• Acute liver failure (increased consumption of
coagulation factors) → DIC

39. Disseminated intravascular
coagulation syndrome (DIC)
• Sepsis and severe infection
• · Trauma (neurotrauma)
• · Organ destruction (eg, pancreatitis)
• · Malignancy (solid and lymphoproliferative/myeloproliferative malignancies)
• · Severe transfusion reactions
• · Obstetric complications – Amniotic fluid embolism; abruptio placentae;
hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; eclampsia
• · Retained dead fetus syndrome
• · Vascular abnormalities - Kasabach-Merritt syndrome and large vascular
aneurysms
• · Severe hepatic failure
• · Severe toxic reactions - Envenomations, transfusion reactions, and transplant
rejection
• · Heat stroke and hyperthermia
• · Hemorrhagic skin necrosis (purpura fulminans) [7, 8]
• · Catastrophic antiphospholipid syndrome (rare) [9]

40. Stages of DIC
There are three stages in DIC syndrome :
1. Stage of hypercoagulation and thrombosis
2. The stage of consumption coagulopathy
3. Stage hypocoagulation

42. Complications of DIC include the
following:
• Acute kidney injury
• Change in mental status
• Respiratory dysfunction
• Hepatic dysfunction
• Life-threatening thrombosis and hemorrhage (in
patients with moderately severe–to–severe DIC)
• Cardiac tamponade
• Hemothorax
• Intracerebral hematoma
• Gangrene and loss of digits
• Shock
• Death

43. HYPERCOAGULABILITY STATES
• A. Primary Hypercoagulability:
• Mutations of factor V (factor V Leiden)
• Protein C deficiency
• Protein S deficiency
• Antithrombin III deficiency
• Hyperhomocysteinemia (may caused by deficiency
and abnormal metabolism of vitamines B9 and B12)
• B. Secondary Hypercoagulability:
• Increased PLATELET function
• Icreased CLOTTING activity
• Both

44. Increased PLATELET function
• Etiology:
• 1) atherosclerosis;
• 2) smoking;
• 3) diabetes mellitus;
• 4) hyperlipidemia/obesity;
• 5) increased platelet count (thrombocytosis > 1.000.000 /
mm3);
• 6) malignancies
• Flow disturbances and endothelial damage
• Increased sensitivity of platelets to factors that induce
adhesiveness/aggregation.
• Type of thrombosis: ARTERIAL, white thrombi (platelets and
little fibrin).
• Complications: ischemia and Infarction.

45. Increased CLOTTING activity
• Etiology:
• - Postsurgical states
• - Prolonged immobility
• - Pregnancy and puerperium (postpartum period)
• - Congestive heart failure
• - Malignant disease
• - Sepsis
• Blood stasis, responsible for:
• Accumulation of activated clotting factors
• Prevention of their interaction with the inhibitors
• Increased release of tissue factor by tumor cells.
• Type of thrombosis: VENOUS, red thrombi (few platelets,
fibrin, and trapped RBCs).
• Complications: embolism

46. Thank you for your attention!
Email me if you have any questions.
ev.arsenteva@yandex.ru