CHAPTER 1 - HEMOSTASIS PART 3 Flashcards
Severe bleeding from loss of blood from a damaged blood vessel.
hemorrhage
- hemorrhage Types:
a. Localized
b. Generalized
c. Congenital
d. Von Willebrand Disorder
e. Vitamin K Deficiency
bleeding from a single location
Localized
bleeding from multiple sites; often spontaneous, sometimes recurring
Generalized
Ex. Dengue (low platelet)
Generalized
- Mucocutaneous aka
Systemic haemorrhage
Mucocutaneous includes:
Petechiae
Purpura
Ecchymoses
: pinpoint hemorrhage
Petechiae
: purple lesions
Purpura
: bruises greater than 1 cm
Ecchymoses
all are due to trauma
Mucocutaneous
failure in primary hemostasis (blood vessels and platelets)
Mucocutaneous
failure in the secondary hemostasis entire body
Anatomic
lack in 1 Cf may lead to clotting problems over the entire body
Anatomic
since birth
с. Congenital
due to qualitative disorders of blood cell and
blood vessels
с. Congenital
very vital in forming coagulation factor
e. Vitamin K Deficiency
Factor II, VII, IX, X will not be produced if this is absent
e. Vitamin K Deficiency
VASCULAR DISORDERS
- Hereditary Hemorrhagic Telangiectasia aka
“Osler-Weber-Rendu” Disease
- Hereditary Hemorrhagic Telangiectasia
-Cause:
Genetic mutations in the genes
-Autosomal dominant inheritance
- Hereditary Hemorrhagic Telangiectasia
- Hereditary Hemorrhagic Telangiectasia
-Characterized by:
thin walled, disorganized, and dilated BV with discontinuous endothelium= red pinpoint lesions.
- Hereditary Hemorrhagic Telangiectasia
-Laboratory tests:
Bleeding time, platelet function test, CFT and CT are all NORMAL
- Congenital Hemangiomata (Kasabach-Meritt Syndrome)
-Cause:
Protruding tumors composed of blood vessels that swells and bleed.
-Indicative of diffuse DIC
- Congenital Hemangiomata (Kasabach-Meritt Syndrome)
- Other Vasculopathies and their pathophysiology
A. Multiple Myeloma
B. Systemic Amyloidosis
C. Moyamoya Disease
: Light chain immunoglobulin crystalline deposits in the BV
A. Multiple Myeloma
: Amyloid protein with light chain Ig deposits in the BV
B. Systemic Amyloidosis
: Blockage of arteries at the base of the brain
C. Moyamoya Disease
: Fragile arterioles
D. Cerebral small Disease
: inflamed blood vessels.
VASCULITIS
VASCULITIS
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
- Cryoglobulinemia
-Seen in SLE and Wegener’s Granulomatosis.
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
- associated with cryoglobulin immune deposits.
- Cryoglobulinemia
- seen in Waldenstrom’s primary macroglobulinemia
- Cryoglobulinemia
- PIt count is normal, plt adhesiveness is abnormal, FVIll is low.
- Cryoglobulinemia
- Hypergammaglobulinemic Purpura
- characterized by
polyclonal hypergammaglobulinemia
- Hypergammaglobulinemic Purpura- seen in
Sjorgen’s syndrome and SLE, even in Hepatitis C
- Triggers of purpura attack :
- Prolonged walking and standing
- alcohol consumption
- tight-fitting clothes
- otherwise known as
“Purpura rheumatica/anaphylactoid purpura”
-occurs in children between 4-11 years old.
- Henoch-Schonlein Purpura
-characterized by reddish purple spots that looks like bruises.
- Henoch-Schonlein Purpura
VASCULAR OBSTRUCTION
- Thrombus
- Emboli
- Other Occlusions
- Thrombus COMPONENT
-Blood clot
- Emboli COMPONENT
-Septic emboli
-Thromboemboli
- Other Occlusions
a. Immunoglobulins
b. Plasma Proteins
c. Fibrin
d. Red blood cells
e. Platelets
f. Fats
- Thrombus DISEASE CAUSED
-DIC
- Emboli DISEASE CAUSED
-Endocarditis
-Atrial Fibrilation
3. Other Occlusions:
a. Immunoglobulins
-Waldenstrom’s Primary Macroglobulinemia
b. Plasma Proteins
-Cryoglobulinemia
c. Fibrin
-Cryofibrinogenemia
d. Red blood cells
-Polycythemia
e. Platelets
-Thrombocytosis
-Fat emboli syndrome
f. Fats
-group of rare connective tissue disorders caused by collagen synthesis or processing abnormalities.
- Ehlers-Danlos Syndrome
-excessive bruising and bleeding (greatest in EDS type
- Ehlers-Danlos Syndrome Type 4
-prone to arterial aneurysms and dissection, significant bleeding from spontaneous rupture of medium sized abdominal arteries and intestinal rupture.
- Ehlers-Danlos Syndrome
- Ehlers-Danlos Syndrome screening test:
Skin biopsy
- Ehlers-Danlos Syndrome result:
1) No hemostatic abnormality (normal plt, CF, and bleeding time) but with bleeding
2) Abnormal bone extension
- Pseudoxanthoma Elasticum
-also known as
“Groenblad Strandberg Syndrome”
-inherited connective tissue disorder resulting from calcification and mineralization of elastic fibers.
- Pseudoxanthoma Elasticum
-autosomal recessive inheritance
- Pseudoxanthoma Elasticum
- Pseudoxanthoma Elasticum -autosomal recessive inheritance (gene involved ?)
ABC-C6 gene
-development of narrowing arteries (arteriosclerosis) or “claudication”
- Pseudoxanthoma Elasticum
narrowing arteries (?) or
arteriosclerosis
characterized by cramping and pain during exercise because of decreased blood flow to the arms and legs.
claudication
- Characterized by absence of Vitamin C
- Scurvy
-Weakened collagen strands as a result of abnormal triple helical structure.
- Scurvy
- Scurvy -Predisposes patients to
capillary fragility, delayed wound healing, petechiae and purpura, oral, urinary and digestive bleeding.
promotes activation of procollagen to collagen
Vitamin C
- Senile Purpura
-otherwise known as
“Solar purpura”
-commonly found on hands and forearms without any known preceding trauma
- Senile Purpura
-thin skin as a result of loss of subcutaneous fat and changes in both amount and quality of
- Senile Purpura
- Senile Purpura-Hemostasis tests are
NORMAL
- Purpura associated with Infections
(?) caused by microbial agents associated with (?) producing petechiae.
-direct endothelial cell damage
acute febrile illness
- Purpura associated with Infections
-Bacterial toxins produce deendothelization induced by an
endotoxin
- Purpura associated with Infections-commonly known diseases:
- Rickettsial disease
- Brazilian purpura fever
- Rat bite fever
- Vibrio vulnificus infection
- Strongyloides
- Acquired purpura Fulminans
- Acute infectious purpura fulminans
- causes by varicella zoster virus
- Acquired purpura Fulminans
- caused by any gram negative bacteria
- Acute infectious purpura fulminans
-can be a result of
contact dermatitis, steroid use, drug reactions or allergies
- Purpura related to miscellaneous causes
-some may be observed in
Kaposi sarcoma and vascular tumors.
occurs in women during menstrual period
Purpura simplex
Purpura simplex also known as
“factitious or self-imposed purpura”
Purpura simplex Types:
a. Anaphylactoid purpura
b. Henoch’s
c. Schonlein’s
Promotes vasoconstriction
CONSTRICTOR
Dilates the blood vessels; widens the lumen; reestablishes blood flow
DILATOR
CONSTRICTOR
ENDOTHELIN-I
ANGIOTENSIN-I
PROSTAGLANDIN
DILATOR
PROSTACYCLIN
NITRIC OXIDE
ENDOTHELIUM DERIVED RELAXING FACTOR (EDFR)
: blood vessel disorders
VASCULAR DISORDER
very vital in forming coagulation factor
Vitamin K
will not be produced if Vitamin K is absent
Factor II, VII, IX, X
- Genetic disorder
- Hereditary Hemorrhagic Telangiectasia
- Autosomal dominant: needs at least 2 dominant genes from the parents to manifest (Ex. AA cannot manifest the disease since it is recessive)
- Hereditary Hemorrhagic Telangiectasia
- cause: reduced amount of functional protein in the tissue lining of the bv
- Hereditary Hemorrhagic Telangiectasia
- endothelium lacks protein due to the genetic mutation in the following genes:
- ENG gene (TYPE 1 HHT)
- ACVRL gene (TYPE 2 HHT)
- SMAD 4 (JUVENILLE TYPE)
- Unknown (TYPE III HHT)
– growing but not maturing to that kind of disease or not progressive)
- SMAD 4 (JUVENILLE TYPE)
When these genes mutate in the body, it causes proteins to not form in the endothelium
- Hereditary Hemorrhagic Telangiectasia
protein contributes to the integrity of the blood vessels
- Hereditary Hemorrhagic Telangiectasia
one of the most important proteins: tissue factor, collagen
- Hereditary Hemorrhagic Telangiectasia
characterized by thin-walled, disorganized and dilated blood vessels (due to absence of protein in the endothelium)
- Hereditary Hemorrhagic Telangiectasia
Laboratory findings: Bleeding time, platelet function tests, Capillary Fragility test and coagulation tests are all normal
- Hereditary Hemorrhagic Telangiectasia
(no problem on platelet, coagulation factor, but bleeding is due to the problem in the endothelial lining)
- Hereditary Hemorrhagic Telangiectasia
Small widened blood vessels (like ruptured/varicose veins)
telangiectasias?
Exhibit petechiae formation in the mouth
telangiectasias?
Epistaxis (prolonged bleeding due to endothelium)
telangiectasias?
Disorders associated with tumors composed of many entangled blood vessels.
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
Tumor composed of blood vessels that commonly swell and bleed
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
Formation of fibrin clots, platelet consumption and red cell destruction secondary to vascular obstruction occur at the site of tumor
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
indicative of diffuse DIC (disseminated intravascular coagulation)
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
Very lethal disorder
diffuse DIC (disseminated intravascular coagulation)
Coagulation and fibrinolysis happens at the same time
diffuse DIC (disseminated intravascular coagulation)
tumor protrudes from the skin surface
diffuse DIC (disseminated intravascular coagulation)
affects infants/babies
diffuse DIC (disseminated intravascular coagulation)
aka Hemangiomata with thrombocytopenia/Hemangioma thrombocytopenia syndrome
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
swollen blood vessel will clot the blood inside while the platelets are being consumed resulting to thrombocytopenia
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
congenital: dangerous when operating a baby but removing the tumor is possible to repair the bv
- Congenital Hemangiomata (Kasabach-Merritt Syndrome)
- Other Vasculopathies
Light chain immunoglobulin crystalline deposits in the BV
Multiple Myeloma
Production of abnormally large plasma cells that produces many light chains that deposits in the bv, causing fragile vessels
Multiple Myeloma
Portion of the Ab is attacking the blood vessel
Multiple Myeloma
Main problem: production of abnormal plasma cells
Multiple Myeloma
Side effect: vasculopathy or deposition of light chain Ig in the bv
Multiple Myeloma
Even minor trauma causes bleeding to the vessels
Multiple Myeloma
Most specific type of vasculitis: Necrotizing vasculitis (cell damage and death) – w/o marker
Multiple Myeloma
caused by light chain Ig deposition
Multiple Myeloma
Amyloid protein with light chain Ig deposits in the BV
Systemic Amyloidosis
Systemic Amyloidosis TYPES:
AL-Amyloidosis
1o Systemic Amyloidosis
amyloid + ligh chain Ig
1o Systemic Amyloidosis
concerns the skin purpura and skin blisters without co-existing disease
1o Systemic Amyloidosis
more on skin than organ involvement
1o Systemic Amyloidosis
coexisting w/ infection or inflammation
2o Systemic Amyloidosis
amyloid protein and light chain both deposits in the blood vessel
2o Systemic Amyloidosis
no skin; more on organ involvement
2o Systemic Amyloidosis
amyloidosis iseasily diagnosed using
congo red
congo red (also stains smear - w/ high affinity to amyloid proteins - color is)
yellow bifringence
Blockage of arteries at the base of the brain
Moyamoya Disease
main artery in the brain delivers oxygen is blocked
Moyamoya Disease
smaller arteries entangle w/ each other to compensate for oxygen
Moyamoya Disease
entangled bv: “puff of smoke”
Moyamoya Disease
cause of blockage: due to clot or emboli - may cause intracranial haemorrhage or brain infarcts
Moyamoya Disease
Fragile arteries
Cerebral Small Disease
arterioles are so fragile that they tend to burst
Cerebral Small Disease
may suffer from recurrent stroke, mini stroke, cognitive impairment
Cerebral Small Disease
cause: fragile arterioles
Cerebral Small Disease
MRI (white portion): deprived of oxygen
Cerebral Small Disease
- inflamed blood vessels; complement system is activated
Vasculitis
VASCULITIS
neutrophil is dying since ANCA attacks the body’s own neutrophil
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
Ig autoantibody
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
attacks the cytoplasm or or the granule of the neutrophil
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
TYPES:
pANCA
cANCA:
pANCA: - targets the
primary granule (myeloperoxidase)
cANCA: - targets
proteinase 3 (enzyme found in the tertiary granule of the neutrophil) and cytoplasm
WBC is found inside the bv
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
marker of primary necrotizing vasculitis
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA)
- Antineutrophilic Cytoplasmic Antibody Positive (ANCA) - Seen in
Systemic Lupus Erythematosus and Wegener’s Granulomatosis
- Cryoglobulinemia - seen in
Waldenstrom’s Primary Macroglobulinemi a
- Hypergammaglob ulinemic Purpura – seen in
Sjorgen’s syndrome and SLE, even in Hepatitis C
- HenochSchonlein Purpura - aka
IgA Vasculitis or Anaphylactic vasculitis
associated with deposited cryoglobulin
- Cryoglobulinemia
cryoglobulin : protein that precipitates in cold temperature
- Cryoglobulinemia
precipitated protein looks like a soliinsoluble pack in a test tube
- Cryoglobulinemia
hypothermic temp will allow cryoglobulin to precipitate, obstructing the blood vessel
- Cryoglobulinemia
causes: infarcts, ischemia
- Cryoglobulinemia
plt count is normal; plt adhesiveness is abnormal (ptl cannot adhere to a precipitated protein); FVIII is low and will just precipitate
- Cryoglobulinemia
blood is hyperviscous
- Cryoglobulinemia
with many petechiae and purpura
- Cryoglobulinemia
characterized by polyclonal hypergammaglobulinemia
- Hypergammaglob ulinemic Purpura
increased IgG
- Hypergammaglob ulinemic Purpura
once triggered it may lead to purpura attack
- Hypergammaglob ulinemic Purpura
can be very reactive – bv are prone to it
- Hypergammaglob ulinemic Purpura
Triggers of purpura attack:
- Prolonged walking and standing
- alcohol consumption
- tight-fitting clothes
otherwise known as “Purpura rheumatica/anaphylactoid purpura”
- HenochSchonlein Purpura
IgA Vasculitis or Anaphylactic vasculitis
- HenochSchonlein Purpura
Targets OF Anaphylactic vasculitis:
GIT, kidney, skin, lungs, CNS
occurs in children between 4-11 years old.
- HenochSchonlein Purpura
characterized by reddish purple spots that looks like bruises
- HenochSchonlein Purpura
: causes abdominal haemorrhage (more common on the GIT)
Henoch
: causes joint (wrist, ankle) cavities haemorrhage
Schoenlein
Cause: IgA deposition causing vasculitis
- HenochSchonlein Purpura
TYPES OF VASCULAR OBSTRUCTION
Thrombus • Composition:
1) platelets
2) rbc,
3) fibrin
• clot attached to many constituents
Thrombus
• clot attached to many constituents that travels
Emboli
• travels down to the blood vessel that block the blood flow
Emboli
• does not particularly creates a clot but accumulates to be a block
Other Occlusions
• may accumulate and cause obstruction
Other Occlusions
may accumulate and deposit in the bv causing fragility
a. Immunoglobulins
• may form a plaque causing an obstruction
a. Immunoglobulins
• precipitates when exposed to low temp
b. Plasma Proteins
c. Fibrin
• viscous blood when many
Red blood cells
• hyperviscosity may harden the rbcs as cells not as clot
Red blood cells
• may be occluded when many
Platelets
• clot attached to a fat
Fats
• abnormal blood clot is seen
DIC
• DIC complications:
1) excessive clot formation or thrombosis
2) hemolysis
3) fibrinolysis
•: infected clot/abscessed embolism
Septic emboli
• a pure clot that travels
Thromboemboli
• Thrombus that travels
Thromboemboli
• may travel to endocardium leading to endocarditis
Endocarditis
• messes the bv of the heart
Atrial Fibrilation
• irregular rhythm of the heart
Atrial Fibrilation
• dangerous when hypothermic
Cryoglobulinemia
Cryofibrinogenemia
Group of rare connective tissue disorders caused by abnormalities in collagen synthesis
DISORDERS OF PERIVASCULAR TISSUES
Hereditary Connective Tissue Defects
– absence of collagen leads to bleeding
Ehlers-Danlos Syndrome
Vitamin C Deficiency (Scurvy)
- excessive bruising and bleeding
- Ehlers-Danlos Syndrome
- greatest in TYPE 4 EHLERDANLOS/VASCULAR; (may be bone, skin, elastic tissues, blood vessels
- Ehlers-Danlos Syndrome
- prone to arterial aneurysms and dissection
- Ehlers-Danlos Syndrome
- problem in the skin also affects the surrounding tissues, hence affecting the entire vascular system
- Ehlers-Danlos Syndrome
- significant bleeding from spontaneous rupture of medium sized abdominal arteries and intestinal rupture
- Ehlers-Danlos Syndrome
- problem on quantitative or qualitative collagen production defect
- Ehlers-Danlos Syndrome
- collagen is imp in platelet activation affecting hemostasis and perivascular tissues
- Ehlers-Danlos Syndrome
- Ehlers-Danlos Syndrome
- Screening test:
Skin biopsy
- to examine elasticity (too stretchy is abnormal)
Skin biopsy
- Ehlers-Danlos Syndrome
- Result:
1) No hemostatic abnormality (normal plt, CF, and bleeding time) but with bleeding and
2) Abnormal bone extension - fragile skin affects subcutaneous tissue passing fragility to bv
- inherited connective tissue disorder resulting from calcification and mineralization of elastic fiber
- Pseudoxanthoma elasticum
- attached to zinc or copper
- Pseudoxanthoma elasticum
- autosomal recessive inheritance (abnormal 2 recessive genes)
- Pseudoxanthoma elasticum
- gene involved : [?] to produce [?] protein is a vehicle contributing to the release of [?] from the cell and not use it
ABC-C6 gene
MRP6
ATP
is done outside the cell and used to form pyrophosphate from phosphate
- ATP
is a regulator of calcium (4th most abundant intracellular cation); brings the Ca inside the cell to prevent deposition in bv and skin and stop elastic fiber calcification
- Pyrophosphate
- development of narrowing arteries (arteriosclerosis) or “claudication”, characterized by cramping and pain during exercise because of decreased blood flow to the arms and legs
- Pseudoxanthoma elasticum
: fat emboli; artery blocked byb fat
- Athros
: narrowing of artery
- Arterios
- Characterized by absence of Vitamin C
- Vitamin C Deficiency (Scurvy)
- promotes activation of procollagen (zymogen; inactivated) to collagen
- Vitamin C Deficiency (Scurvy)
- Weakened collagen strands as a result of abnormal triple helical structure.
- Vitamin C Deficiency (Scurvy)
- Vitamin C Deficiency (Scurvy)
- Predisposes patients to
1) capillary fragility, 2) delayed wound healing, 3) petechiae and 4) purpura, and 5) bleeding (oral, urinary and digestive)
–predisposed to more thrombosis than bleeding (they are anemic; wound healing is slow; other processing of the body is delayed)
- Senile Purpura
- common in elders
- Senile Purpura
- commonly found on hands and forearms without any known preceding trauma
- Senile Purpura
- thin skin as a result of loss of subcutaneous fat and changes in both amount and quality of collagen (quality of collagen decreases when aging)
- Senile Purpura
- Hemostasis tests are normal
- Senile Purpura
• Direct endothelial cell damage caused by microbial agents associated with febrile illness producing petechiae
- Pupura associated with infections
• commonly known diseases:
- Rickettsial disease
- Brazilian purpura fever
- Rat bite fever
- Vibrio vulnificus infection
- Strongyloides
- causes by varicella zoster virus
- Acquired purpura Fulminans
- caused by any gram negative bacteria
- Acute infectious purpura fulminans
• bacterial toxins produce deendothelization induced by
endotoxin
• can be a result of contact dermatitis, steroid use, drug reactions or allergies
- Purpura related to miscellaneous causes
• some may be observed in Kaposi sarcoma and vascular tumors.
- Purpura related to miscellaneous causes
occurs in women during menstrual period.
Purpura simplex
Purpura simplex
• Also known as “factious or self-imposed purpura”
Purpura related to miscellaneous causes Types:
a. Anaphylactoid purpura
b. Henoch’s
c. Schonlein’s
• Sex-linked
Ehlers-Danlos Syndrome
Caused by a defect in peptidase enzyme that converts procollagen to collagen
Ehlers-Danlos Syndrome
• Characterized by hyperextensive joints and hyperplastic skin
Ehlers-Danlos Syndrome
• Laboratory findings: Normal Coagulation test and platelet function studies
Ehlers-Danlos Syndrome
Autosomal recessive
Pseudoxanthoma elasticum
Characterized by calcified and structurally abnormal elastic fibers
Pseudoxanthoma elasticum
for the formation of the intact structure of the vascular basement membrane
vitamin C
• Characterized by gingival bleeding
Vitamin C Deficiency (Scurvy)
hemorrhage into subcutaneous tissues and muscles
Vitamin C Deficiency (Scurvy)
Large hemorrhagic areas may develop just below the eyes
Vitamin C Deficiency (Scurvy)
splinter-like hemorrhage may also appear in the fingernail beds
Vitamin C Deficiency (Scurvy)
splinter-like hemorrhage may also appear in the fingernail beds
Vitamin C Deficiency (Scurvy)
Laboratory findings: CFT= usually positive
Vitamin C Deficiency (Scurvy)
Related with normal aging process
Senile Purpura
• Laboratory findings: CFT= positive; Bleeding time= normal or only slightly prolonged
Senile Purpura
• Deposition of glycosylated proteins leading to thickening of capillary basement membrane affecting often the capillaries of the renal glomeruli and retina
Diabetes Mellitus
• Excessive amyloid deposit in small vessels
Amyloidosis
Autoimmune Vascular Purpura types
a. Drug Induced Purpura
b. Allergic purpura/Anaphylactoid purpura
• associated with certain foods and drugs, cold temperature, insect bites and vaccinations.
b. Allergic purpura/Anaphylactoid purpura
• Henoch’s Purpura = associated with
abdominal pain secondary to GIT hemorrhaging
• Schonlein’s Purpura = associated with
joint, especially in the knees, ankles and wrists
• Common drugs that induce purpura: sulfonamides & iodides quinine, procaine, penicillin, aspirin, sedatives, coumarin
Drug Induced Purpura
• May be due to development of antibodies to vessel wall components, development of immune complexes, and changes in vessel wall permeability.
Drug Induced Purpura
• Associated with bacterial; viral, Rickettsial and protozoal infections.
Infectious Purpura
