4 - Bruising Flashcards
What are the learning objectives of Chapter 4?
- Discuss different types of easy bruisability and their causes
- Discuss the three general components of hemostasis
- Describe the formation of primary and secondary hemostatic plugs
- Describe the resolution of a hemostatic plug
- Compare and contrast the initiation of thrombin formation by intrinsic and extrinsic pathways
- Explain why the activation of the clotting cascade does not coagulate all blood in the body
- List the organ systems associated with easy bleeding/bruising
- Discuss common hematologic laboratory abnormalities associated with bleeding disorders
- Differentiate causes of easy bleeding/bruising given key clinical features
- Develop a differential diagnosis for easy bleeding/bruising
- Compare mechanisms of anticoagulation of heparin and warfarin
What percentage of healthy patients have experienced epistaxis, easy bruising, or bleeding gums?
Approximately 26%-45%
What is the definition of bleeding?
Blood loss when blood vessels are injured due to trauma or injury
What is the definition of bruising?
Blood leaks into the subcutaneous area where the outer skin is injured but not lacerated or broken
What are the types of bleeding and bruising?
- Pinpoint cutaneous hemorrhage
- Massive external bleeding
- Internal hemorrhage
Where should bruises raise suspicion for physical abuse?
- Ears
- Neck
- Feet
- Buttocks
- Chest
- Back
- Abdomen
- Genitalia
What is hemostasis?
The body’s response to control bleeding
What are the two classifications of pathologic entities of hemostasis?
- Acquired
- Hereditary
What is the term for a tendency toward a problem such as a bleeding diathesis?
Diathesis
What is a contusion?
Bruise
Define ecchymoses.
Largest hemorrhagic lesions under the skin, diameter larger than 10 mm
What is an embolus?
A floating intravascular clot
What is epistaxis?
Nose bleed
What is a hematoma?
A blot clot in a tissue or organ due to a ruptured blood vessel
What is hemarthrosis?
Bleeding into joints
What does the International normalized ratio (INR) measure?
It standardizes the assessment of prothrombin time
What is the normal INR value?
1.0
What does a prolonged partial thromboplastin time (PTT) suggest?
An intrinsic disorder in clotting
What is the diameter range for petechiae?
1-2 mm
What is purpura?
Hemorrhagic lesions larger than petechiae, diameter 2-10 mm
What is primary hemostasis?
Platelet plug formation at the site of vascular injury
What does prothrombin time (PT) assess?
The ability of the extrinsic pathway to form a clot
What is telangiectasia?
Small dilated blood vessel noted on skin or mucous membranes
What are Weibel-Palade bodies?
Secretory specialized organelles of endothelial cells containing von Willebrand factor
What is von Willebrand factor (vWF)?
A glycoprotein that mediates adherence to subendothelial tissue and acts as a carrier for factor VIII
What is a common clinical impression for a patient with a bleeding disorder?
The history supports a bleeding disorder that has been non-life-threatening
What laboratory values are important for differential diagnosis of bleeding disorders?
- Prothrombin time (PT)
- Partial thromboplastin time (PTT)
What is a common inherited bleeding disorder?
von Willebrand disease (vWD)
What distinguishes hemophilia from von Willebrand disease?
Hemophilia is X-linked recessive, while vWD is autosomal dominant
What are the two common types of hemophilia?
- Hemophilia A (factor VIII deficiency)
- Hemophilia B (factor IX deficiency)
What is Glanzmann thrombasthenia?
An autosomal recessive disorder resulting from defective glycoprotein IIb/IIIa
What is Bernard-Soulier syndrome?
A rare autosomal recessive disorder resulting from the absence of glycoprotein Ib receptor for vWF
What is pseudo von Willebrand disorder characterized by?
Hyperresponsive platelets leading to thrombocytopenia
What can cause acquired von Willebrand disease?
Formation of anti-vWF antibodies associated with various disorders
What does the presence of thrombocytopenia and low levels of vWF and factor VIII suggest?
A diagnosis of von Willebrand disease
What is von Willebrand disease (vWD)?
A bleeding disorder characterized by low levels of von Willebrand factor (vWF), leading to impaired platelet adhesion and aggregation
vWD can present with mucosal and cutaneous bleeding symptoms.
What laboratory findings support a diagnosis of vWD?
Low levels of vWF, low factor VIII levels, and thrombocytopenia
The presence of multiple family members with a bleeding diathesis also supports this diagnosis.
Why might vWF levels be borderline low instead of extremely depressed?
vWF can be temporarily elevated during stress from acute bleeding events, but still low enough to cause clinical symptoms.
What are the management options for vWD?
Administration of desmopressin, recombinant vWF, and vWF along with factor VIII infusions in severe cases.
What is hemostasis?
The process that stops bleeding from a damaged vessel while maintaining normal blood flow elsewhere in circulation.
What are the two main components of hemostasis?
Primary hemostasis and secondary hemostasis.
What are the four steps involved in primary hemostasis?
- Vasoconstriction
- Platelet adhesion
- Platelet activation/degranulation
- Platelet aggregation
What role does endothelin play in primary hemostasis?
It is a hormone secreted by damaged endothelial cells that causes vasoconstriction.
What is the function of von Willebrand factor (vWF)?
It mediates adhesion of platelets to subendothelial collagen and carries factor VIII, stabilizing it in circulation.
What are platelets?
Cell fragments derived from megakaryocytes in the bone marrow, essential for clot formation.
What are the two types of granules found in platelets?
- Alpha granules
- Dense granules
What do alpha granules contain?
vWF and fibrinogen, which are important for platelet aggregation.
What is the role of nitric oxide and prostacyclin in platelet aggregation?
They act as vasodilators and inhibit platelet adhesion under normal physiological conditions.
How are platelets activated?
Through adhesion to collagen, leading to shape change and aggregation via GPIIb/IIIa receptor.
What happens if von Willebrand factor is defective?
There is little or no platelet adhesion or aggregation, impacting both primary and secondary hemostasis.
What is the historical significance of von Willebrand disease?
Identified by Finnish physician Erik von Willebrand in the early 1900s through his observations of a family with bleeding disorders.
What are other diseases that involve primary hemostasis?
Disorders such as Glanzmann thrombasthenia and other genetic disorders of primary hemostasis.
What is d-Dimer?
A fibrin degradation product important for detecting activation of coagulation and fibrinolysis.
What is secondary hemostasis?
Activation of the intrinsic and extrinsic coagulation pathways to produce a stable fibrin mesh.
What condition does compartment syndrome refer to?
Bleeding into a closed space in the muscles, leading to ischemia and potential damage.
What differential diagnoses are considered with normal platelet count?
Exclusion of cirrhosis, hematologic malignancies, and idiopathic thrombocytopenic purpura.
What is the most likely diagnosis among clotting factor deficiencies based on relative frequency?
Factor VIII deficiency.
Fill in the blank: The repeat vWF level after an incident of bleeding showed a level in the range of _______.
[mild to moderate disease]
What conditions are ruled out due to a normal platelet count?
Ologic malignancies and idiopathic thrombocytopenic purpura
Normal platelet count excludes these conditions.
What does a normal prothrombin time indicate?
Excludes vitamin K deficiency syndromes
It suggests that von Willebrand disease and intrinsic pathway clotting factor deficiencies are more likely.
Which clotting factor deficiency is most likely based on relative frequency?
Factor VIII deficiency
This is considered the most likely diagnosis among clotting factor deficiencies.
What laboratory tests are requested to confirm factor VIII deficiency?
Levels for factor VIII and vWF
These tests help in diagnosing hemophilia A.
How is factor VIII deficiency characterized in terms of severity?
Moderate deficiency is indicated by a factor VIII level of 4.0%
This level explains the delayed onset of symptoms.
What is the genetic inheritance pattern of classic hemophilia A?
X-linked recessive disorder
It may also arise due to spontaneous mutation in about one-third of cases.
What is acquired hemophilia?
A rare autoimmune disorder causing factor VIII deficiency
It develops antibodies against factor VIII due to triggering events.
Which symptoms of hemophilia become pronounced at factor VIII levels of 1% or below?
Hemoptysis, hematemesis, epistaxis, hemarthrosis, hematuria, CNS bleeding, compartment syndromes
These symptoms are proportional to the level of circulating factor VIII.
What are the factor levels associated with moderate and mild hemophilia?
Moderate: 1%-5%; Mild: 6%-30%
Mild symptoms may not occur until adulthood.
What distinguishes hemophilia B from hemophilia A?
Hemophilia B is caused by factor IX deficiency
Both hemophilia B and A are X-linked disorders.
What is the treatment for hemophilia A?
Administration of genetically engineered recombinant factor VIII
Desmopressin can be used in milder cases to increase vWF and factor VIII.
What can develop due to recombinant factor VIII treatment?
Autoantibodies against factor VIII, known as factor VIII inhibitors
These can neutralize the effects of factor VIII supplementation.
What is the role of thrombin in hemostasis?
Activates the coagulation cascade and inhibits overcoagulation
Thrombin also plays a role in anticoagulation and fibrinolysis.
What is the process of fibrinolysis?
Dissolution of clots by plasmin
Plasmin is activated from plasminogen by thrombin and tPA.
What are the two main pathways of the coagulation cascade?
Extrinsic pathway and intrinsic pathway
Both pathways lead to thrombin activation and clot formation.
What triggers the extrinsic pathway of coagulation?
Exposure of blood to tissue factor (TF)
This pathway activates factor VII and leads to rapid clot formation.
How does the intrinsic pathway initiate?
Activated by thrombin from the extrinsic pathway
It amplifies the coagulation process.
What is the common pathway in coagulation?
Activation of factor X to factor Xa
This pathway merges the extrinsic and intrinsic pathways.
What are the consequences of excessive clotting?
Hypercoagulation leading to thrombus formation
This can block blood vessels and requires careful management.
What is disseminated intravascular coagulation (DIC)?
A complication of underlying diseases leading to constant coagulation activation
It results in exhaustion of coagulation factors and increased bleeding tendencies.
Why is the extrinsic pathway insufficient to prevent bleeding in hemophilia A?
It is faster but not robust enough to produce sufficient fibrin
Crosstalk between pathways indicates a reliance on the intrinsic pathway for effective clot formation.
What is the role of desmopressin in hemophilia treatment?
Increases vWF levels and subsequently factor VIII
It is particularly useful for milder cases.
What are the symptoms of von Willebrand disorder compared to hemophilia?
vWD has more mucosal, ecchymotic, and epistatic bleeding
Hemophilia tends to present with joint and deep tissue bleeding.
What should be considered if a hemophilia patient does not respond to treatment?
Inhibitors blocking the effects of factor VIII replacement therapy
This may indicate the presence of factor VIII inhibitors.
What are the three types of bleeding mentioned?
osal, ecchymotic, and epistatic bleeding
How is Factor VIII protected from degradation in serum?
By being bound to vWF
What should be considered if a patient with hemophilia and active bleeding does not respond to therapy?
Inhibitors blocking the effects of factor VIII replacement therapy
What is a significant finding in the physical examination of the 50-year-old man?
A large ecchymotic area on his thigh and multiple spider angiomas
What does the patient’s history of hepatitis B and cirrhosis suggest about his condition?
It suggests cirrhosis secondary to hepatitis B
What does the laboratory findings reveal in the case?
Prolonged prothrombin time and elevated ammonia levels
What does nonresponse to vitamin K supplementation indicate about the liver’s metabolic status?
Severe impairment of hepatic synthetic function
What are some common causes of vitamin K deficiency?
- Inadequate intake
- Malabsorption (e.g., cystic fibrosis, celiac disease)
- Decreased synthesis by enteric bacteria
- Decreased uptake due to liver disease
Fill in the blank: Vitamin K plays a role as a _______ in the carboxylation of glutamate residues.
cofactor
True or False: Vitamin K is primarily obtained from dietary sources only.
False
What is the role of bile salts in the absorption of vitamin K?
They allow vitamin K to be passively transported into the intestinal enterocytes
What is the vitamin K cycle?
The recycling of reduced vitamin K back to its reduced form by VKOR and vitamin K reductase
What does the presence of splenomegaly indicate in this patient?
It leads to low levels of platelets affecting primary hemostasis
What is the primary function of vitamin K in the body?
To act as a cofactor for the posttranslational modification of proteins involved in blood clotting
What is the significance of the patient’s muscle wasting?
It indicates poor nutritional status due to loss of normal hepatic function
What is a potential consequence of administering antibiotics long-term in this patient?
Decreased production of vitamin K
What is the clinical impression of the case regarding liver function?
Loss of normal hepatic function and nutritional balance
What is the role of gamma carboxylation of proteins?
It is essential for the biological functions of these proteins.
Which coagulation factors are gamma carboxylated?
- Factors X
- IX
- VII
- II
- Protein S
- Protein C
How can you remember the vitamin K dependent coagulation factors?
By the mnemonic ‘1972’ where 1 represents 10, then factors IX, VII, and II.
What is the consequence of vitamin K deficiency?
It leads to coagulation defects.
What are the usual laboratory findings with vitamin K deficiency?
- Increased prothrombin time (PT)
- Normal partial thromboplastin time (PTT)
What does warfarin inhibit?
Vitamin K epoxide reductase (VKOR).
What is the therapeutic use of warfarin?
Anticoagulant therapy for venous thrombosis and pulmonary embolism.
What is the therapeutic index of warfarin?
Very narrow.
What is the goal INR range for patients on warfarin?
2.0-3.0.
What is the antidote for bleeding in warfarin therapy?
Vitamin K, fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs).
What are indirect inhibitors of the clotting factors?
Coumadin and heparin.
What is acrodynia?
Painful and tender distal aspects of the digits in the hands and feet.
What is the chemical name of vitamin C?
Ascorbic acid.
What is the function of peptidyl-prolyl-4-hydroxylase?
Essential for collagen synthesis and proper folding of procollagen chains.
What are classic symptoms of vitamin C deficiency?
- Bruising
- Purpura
- Fatigue
- Malaise
- Myalgias
- Bone pain
- Perifollicular hemorrhage
- Corkscrew hair
- Bleeding gums
- Loss of teeth
How does vitamin C deficiency affect blood vessels?
Compromises their integrity due to its role in collagen synthesis.
What is the typical clinical presentation of vitamin C deficiency?
- Anemia
- Bruising
- Bone pain
- Perifollicular hemorrhage
- Corkscrew hair
- Bleeding gums
- Loss of teeth
What are the main functions of vitamin C?
- Antioxidant
- Cofactor for enzymes
- Collagen synthesis
- Carnitine synthesis
- Neurotransmitter synthesis
- Iron absorption
How does vitamin C assist in collagen proper folding?
By hydroxylating proline and lysine residues to stabilize the triple helix structure.
What can prolonged vitamin C deficiency lead to if untreated?
- Poor wound healing
- Multiple fractures
- Neuropathy
- Seizures
- Sudden death
What is the significance of a lengthened prothrombin time (PT) in liver dysfunction?
It is an ominous prognostic indicator.
What are the dietary sources of vitamin C?
Citrus fruits and many colored vegetables.
What is the relationship between vitamin C and catecholamines?
Vitamin C is a cofactor required for their synthesis.
What happens to iron absorption in the presence of vitamin C deficiency?
Nonheme iron absorption is reduced.
How does vitamin C help in the recycling of vitamin E?
By donating electrons to vitamin E.
What is the role of vitamin C in neurotransmitter synthesis?
It acts as a cofactor in the synthesis of serotonin and norepinephrine.
What is modified to hydroxylysine by lysyl hydroxylase?
Lysine
Hydroxylysine is crucial for collagen assembly
What role does vitamin C play in collagen assembly?
Cofactor in crosslinking collagen fibrils
Vitamin C is essential for strong collagen structure
What are classic findings of vitamin C deficiency?
- Bruising
- Bleeding gums
- Loss of dentition
- Perifollicular hemorrhage
- Corkscrew hair
These signs suggest scurvy
What is Cushing disease?
Symptoms of hypercortisolism due to excess ACTH secretion from a pituitary adenoma
What is Cushing syndrome?
Any cause of hypercortisolism, including Cushing disease and adrenal hypersecretion
What is hirsutism?
Excess growth of hair on the body, often male pattern in females
What does the inferior petrosal sinus drain into?
Inferior jugular vein
What is pseudo-Cushing disorder?
Cushing-like symptoms seen in depression and alcoholism
What are striae?
Longitudinal depressions in the skin often occurring in weight gain and Cushing syndrome
What is the clinical impression for diagnosing multiple bruises?
Consider platelet disorders like von Willebrand disease first
What is metabolic syndrome?
A cluster of conditions including obesity, hypertension, glucose intolerance, and elevated serum lipids
What is the significance of the low-dose dexamethasone suppression test?
It helps determine if cortisol secretion is under feedback control
What does a high serum ACTH level indicate?
ACTH-dependent hypercortisolism, consistent with pituitary adenoma or ectopic ACTH-secreting tumor
What is the most common cause of endogenous Cushing syndrome?
Pituitary corticotroph adenomas, known as Cushing disease
What is the role of cortisol under normal physiological conditions?
Maintains homeostasis, involved in metabolism and stress response
What are possible ramifications of long-term steroid therapy?
- Suppression of hypothalamic-pituitary-adrenal axis
- Increased risk of osteoporosis
- Inability to respond to stress
Can lead to catastrophic adrenal crisis
How is cortisol secretion regulated?
Through the hypothalamic-pituitary-adrenal (HPA) axis
Fill in the blank: Vitamin C is a necessary cofactor in the _______ of collagen fibrils.
crosslinking
True or False: Cushing syndrome can only be caused by Cushing disease.
False
What are the findings that suggest a diagnosis of Cushing syndrome?
- Moon facies
- Central obesity
- Easy bruisability
- Abdominal striae
These findings indicate excess cortisol effects
What is the primary physiological role of cortisol?
Cortisol is involved in glucose metabolism and other physiological processes such as stress, energy homeostasis, and body temperature regulation.
Cortisol is the major hormone in humans within the glucocorticoid class.
What are the main components of the adrenal glands?
The adrenal glands are composed of the adrenal cortex and adrenal medulla.
The adrenal medulla synthesizes catecholamines, while the cortex produces corticosteroid hormones.
What do mineralocorticoids primarily regulate?
Mineralocorticoids regulate electrolyte and water balance by increasing sodium absorption and potassium secretion by the kidneys.
What is the effect of glucocorticoids on muscle and fat during stress?
Glucocorticoids promote muscle proteolysis and fatty acid mobilization, leading to muscle wasting and fat deposition in specific areas.
This results in a characteristic appearance known as ‘buffalo hump’ and ‘moon facies’.
How does cortisol affect blood glucose levels?
Cortisol increases blood glucose levels by promoting gluconeogenesis and decreasing cellular uptake of glucose by insulin-dependent transporters.
What happens to protein synthesis in the presence of high cortisol levels?
Protein synthesis is suppressed at the level of translational initiation, leading to thin skin and increased bruising.
How do glucocorticoids exert their physiological effects?
Glucocorticoids exert their effects through transcription of genes via glucocorticoid receptors in the cytoplasm.
What is Cushing syndrome characterized by?
Cushing syndrome is characterized by uncontrolled hypertension, glucose intolerance, thinning of the skin, moon facies, buffalo hump, early osteoporosis, and bruising.
What is the relationship between ACTH and cortisol in Cushing disease?
Cushing disease refers to the excess production of ACTH leading to hypersecretion of cortisol.
What is the feedback mechanism for cortisol regulation?
Cortisol negatively regulates its own secretion by inhibiting ACTH production from the pituitary gland.
What is the most common etiology for Cushing syndrome?
Long-term exogenous administration of cortisone is the most common etiology for Cushing syndrome.
What is an addisonian crisis?
An addisonian crisis occurs when cortisol is withdrawn in a patient who has received long-term cortisone therapy, especially during a stressful clinical issue.
What does the presence of hirsutism in Cushing syndrome indicate?
The presence of hirsutism suggests additional androgen release, indicating a possible neoplasm as the source.
What is an endogenous ectopic source of ACTH?
Rare neoplasms in the lung or other locations can act as an endogenous ectopic source of ACTH, leading to Cushing syndrome.
Cushing syndrome increases the risk of which complications?
Cushing syndrome increases the risk of bruising and bleeding due to downregulation of collagen expression and increased expression of certain clotting factors.
Fill in the blank: Cortisol is best known as a _______.
stress hormone.
True or False: Cortisol promotes wound healing.
False.
What happens to collagen expression in the skin due to high cortisol levels?
High cortisol levels downregulate collagen expression in the skin, leading to thin skin and increased bruising.
What is the primary treatment for an addisonian crisis?
Cortisone replacement is the treatment in an addisonian crisis.
What happens to the levels of factor VIII in Cushing syndrome?
In Cushing syndrome, the expression of factor VIII increases.
What is the significance of glucocorticoid response elements (GRE)?
GRE are DNA elements that glucocorticoid receptor complexes bind to, regulating gene transcription.
How does cortisol affect insulin sensitivity?
Cortisol decreases cellular uptake of glucose by insulin-dependent transporters, leading to increased blood glucose.
What is necessary to ascertain whether a patient is inadvertently eating vitamin K rich foods?
A detailed dietary history.
Understanding a patient’s dietary habits is crucial in managing anticoagulation therapy.
Why is the combination of aspirin and warfarin incorrect?
It would greatly increase the chances of uncontrolled bleeding.
Both are anticoagulants and can significantly raise bleeding risks when used together.
What explains the sudden adrenal insufficiency in a patient with a Cushingoid appearance?
Long-term suppression of adrenal function due to steroid use.
This condition can worsen with sudden lack of prednisone and stress factors.
What is the response time comparison between ACTH and hydrocortisone?
ACTH requires a longer time to respond compared to hydrocortisone.
Hydrocortisone acts quickly to address adrenal insufficiency.
What condition is suggested by the findings of hair, mucosal hemorrhage, bruising, and neuropathy in a child?
Vitamin C deficiency.
These symptoms are indicative of scurvy, a disease caused by lack of vitamin C.
What is the primary deficiency indicated in a malnourished child presenting with specific symptoms?
Vitamin C deficiency.
Other deficiencies could exist, but the specific findings point towards scurvy.
What are the two most common causes of clotting disorders?
- von Willebrand Disease (vWD)
- Factor VIII deficiency
These disorders present similarly with normal PT and abnormal PTT.
What is the inheritance pattern of von Willebrand disease?
Autosomal recessive.
It is important to differentiate this from X-linked disorders like hemophilia.
What is the effect of vitamin C on collagen?
It is important for the folding of collagen into its triple helical conformation.
Vitamin C acts as a cofactor for enzymes that modify collagen.
In Cushing syndrome, what is spared in the liver?
Glycogen degradation.
This leads to increased gluconeogenesis and muscle weakness.
What does high ACTH levels indicate in a patient with physical findings of muscle weakness?
Cushing syndrome due to hypercortisolism.
This condition is characterized by elevated cortisol levels affecting muscle function.
What vitamin is a cofactor for the posttranslational modification of coagulation factors?
Vitamin K.
Deficiency leads to increased PT and PTT due to low levels of several coagulation factors.
What is the primary function of von Willebrand factor (vWF)?
Acts as glue to form an attachment between subendothelial collagen and platelets.
It also stabilizes factor VIII, essential in coagulation.
What is hemophilia A caused by?
A deficiency in factor VIII.
It is an X-linked recessive disorder primarily affecting males.
What does a normal PT and prolonged PTT imply?
Hemophilia A.
This indicates a defect in the intrinsic pathway of coagulation.
What is the relationship between vitamin K and liver function?
Vitamin K is synthesized in the gut but also requires dietary intake.
Deficiency can occur due to poor diet or liver dysfunction affecting coagulation factor synthesis.
What condition is indicated by increased PT and PTT?
Deficiency in the common pathway of coagulation.
Factors involved include X, V, II, and I, often linked to liver disease.
