YL6: 04.

17b Approach to a Patient with Hematologic Alterations

10/10/2019 Basic Pathologies 2
07:30-09:30 Rico Paolo Gomez Tee, MD, FPCP, DPSHBT
CLINICAL MEDICINE

TABLE OF CONTENTS Other Symptoms

• Headache
I. APPROACH TO A PATIENT WITH POLYCYTHEMIA ....................... 1 → Blood may be too thick and cannot circulate so the patient
A. POLYCYTHEMIA.................................................................... 1 experiences a heavy or full feeling
B. MEDICAL HISTORY ............................................................... 1 • Vertigo
C. PHYSICAL EXAMINATION ..................................................... 1 • Aquagenic pruritus
D. LABORATORY TESTS ........................................................... 1 → Itchiness after taking a bath
II. APPROACH TO A PATIENT WITH LYMPHADENOPATHY.............. 2
• Visual disturbance
A. LYMPHOPOIESIS .................................................................. 2
B. LYMPHADENOPATHY ........................................................... 2
C. MEDICAL HISTORY ............................................................... 2 NICE TO KNOW: OTHER SYMPTOMS (Kasper et al., 2015)
D. PHYSICAL EXAMINATION ..................................................... 2 • Dominant symptoms related to increased RBC mass are
E. LABORATORY INVESTIGATION ............................................ 3 related to hyperviscosity and thrombosis
III. APPROACH TO A PATIENT WITH SPLENOMEGALY .................... 3
→ Abdominal vessel thromboses are common
A. SPLENOMEGALY .................................................................. 3
B. PHYSICAL EXAMINATION ..................................................... 3 • Hypertension
C. DISEASES ASSOCIATED WITH SPLENOMEGALY ............... 4 • Easy bruising, epistaxis, or bleeding from GI tract
IV. APPROACH TO A PATIENT WITH WBC ABNORMALITIES ........... 4 • Peptic ulcer disease
A. LEUKEMIA ............................................................................. 4 • Impaired mental faculty
V. APPROACH TO A BLEEDING PATIENT AND A PATIENT WITH • Fatigue
PATHOLOGIC CLOTTING .................................................................. 4 • Tinnitus
A. REVIEW OF HEMOSTASIS AND THROMBOSIS .................... 4
B. DIAGNOSTIC APPROACH TO A BLEEDING PATIENT........... 5
C. DIAGNOSTIC APPROACH TO A PATIENT WITH PATHOLOGIC C. PHYSICAL EXAMINATION
CLOTTING ................................................................................. 6 • Flushing
QUICK REVIEW ................................................................................. 7
→ As mentioned earlier; the appearance of rosy cheeks
SUMMARY OF TERMS .............................................................. 7
MNEMONICS ............................................................................. 8 • Heart murmurs
REVIEW QUESTIONS ................................................................ 8 • Lung sounds
REFERENCES ................................................................................... 8 • Cyanosis on minimal exertion
REQUIRED ................................................................................ 8 → May suggest congenital heart disease
APPENDIX ......................................................................................... 8 • Abdominal pain
FREEDOM SPACE ............................................................................. 9  May be due to abdominal thrombi
• Splenomegaly
 Usually associated with polycythemia vera
I. APPROACH TO A PATIENT WITH POLYCYTHEMIA
A. POLYCYTHEMIA D. LABORATORY TESTS
• The basic mechanism is that the body tries to compensate for • Patients with polycythemia usually present with increased
oxygen depletion by increasing RBC production hemoglobin or hematocrit
• Increase in hemoglobin above normal levels
→ Males: Hgb > 170 g/L
→ Females: Hgb > 150 g/L
→ But according to New WHO guidelines:
▪ Hgb >160 g/L for both males and females

Relative Polycythemia vs. Absolute Polycythemia

 Relative Polycythemia when there is hemoconcentration due to
decreased plasma volume
 Results from dehydration (e.g. water deprivation, prolonged
vomiting or diarrhea, or excessive use of diuretics)
 Absolute Polycythemia when there is an increase in total red
cell mass
 Can be primary or secondary
 Most common cause of primary polycythemia is
polycythemia vera, a disorder that associated with
mutations leading to EPO-independent growth of
progenitor cells

B. MEDICAL HISTORY
• Since the basic mechanism is that the body tries to compensate for
oxygen depletion by increasing RBC production, it is important to
check in the history those that concern oxygen depletion or
hypoxia
Figure 1. Approach to differential diagnosis of patients with elevated
Features of The Clinical History That Are Useful
hemoglobin (Kasper et al., 2015)
• Smoking history
• Living situations at high altitudes Tests Supporting the Diagnosis of Polycythemia Vera
→ Ex: People living in Baguio have rosy cheeks  Elevated WBC count or leukocytosis
• History of congenital heart disease  Increased absolute basophil count
• History of chronic lung disease  Elevated platelet count or thrombocytosis
• History of sleep apnea  Usually with low levels of EPO
→ Breathing is interrupted while sleeping  Due to the increased number of RBCs produced by the bone
→ People at risk of sleep apnea are people with small jaws or marrow (negative feedback)
short neck

YL6: 04.17b Transcribed by TG 16: Balonan, Bondoc, Calanoc, Fernando, Guerrero, Melevo, Vergara, Viernes 1 of 9
 If EPO levels are elevated, one needs to distinguish if this is a
physiologic response to hypoxia or related to autonomous EPO
production
 For example, for smokers with normal oxygen saturation, they
may have elevated EPO because of carbon dioxide
displacement of oxygen and thus high carboxyhemoglobin
(COHb) levels; thus, the diagnosis is Smoker’s Polycythemia
(due to elevated Hb) despite the elevation of EPO.
II. APPROACH TO A PATIENT WITH LYMPHADENOPATHY
A. LYMPHOPOIESIS
• Begins in the lymphoid line
→ Lymphoblast → Lymphocyte → Plasma Cells (produce
immunoglobulin)
Figure 2. Lymphoid Cell Development (Tee, 2019)
B. LYMPHADENOPATHY
Enlargements of The Lymph Nodes
• May just be a benign incidental finding or a presenting sign of an
underlying disease
 Most of the time, they are benign and have non-specific
etiologies
 May be a primary or secondary manifestation of numerous
disorders
→ See Appendix Table 7 for the full list of diseases that Doc
flashed in class
 Physician must eventually decide whether the lymphadenopathy is
a normal finding or one that requires study and biopsy
→ If it is in the neck area and < 1cm in size, it is usually benign
→ In the groin (inguinal lymph node) if it is > 2 cm in size, it is
something that warrants further investigation
Reactive Lymphadenopathy
• Can occur when one has cough and colds or when one has dental
carries
Lymphadenopathy due to Infection
• Can be due to bacterial or viral infections
→ Example of disease of viral etiology: Infectious Mononucleosis
Syndromes (Kissing Disease)
C. MEDICAL HISTORY
• Good medical history and physical exam is needed in patients
presents with lymphadenopathy
Questions to Ask the Patient
• Concurrent illnesses
→ Sore throat
→ Cough
→ Fever
→ [Drenching] Night sweats (very important symptom)
▪ “Kahit naka-aircon na kayo, nagpapawis pa rin ba?”
▪ Can possibly indicate lymphoma
→ Fatigue
→ Weight loss
• Age
→ Children have higher incidences of lymphadenopathies
▪ Because they don’t have much fat yet in the neck and as
such a simple cough or cold results in palpable lymph
nodes
→ In adults, one does not usually see them and as such may be
worth investigating
• Sex
• Personal/Social History
YL6: 04.17b Basic Pathologies 2: Approach to a Patient with Hematologic Alterations
• Sexual History
→ Important given that certain sexually transmitted diseases
may present as lymphadenopathy
WHY THE PRESENCE OF NIGHT SWEATS AND WEIGHT LOSS
ESPECIALLY IN MALIGNANCIES? (Kurzrock, 2001)
• Primarily due to a surge of cytokines (TNF)
• Cancer cells and the immune system appear to overexpress a
range of cytokines
• The release of cytokines into the blood as stimulated by
malignancy triggers a change in the thermoneutral zone → body
then compensates by compensates to lower your core
temperature by sweating → night sweats
• Cancerous cachexia, a wasting syndrome and a hallmark of
cancer can be attributed to loss of appetite or enhanced energy
expenditure
• Thus, nights sweats and weight loss are important things to
note especially in malignancies
D. PHYSICAL EXAMINATION
• Size of Node
• Characteristic
• Tenderness of Nodes
• Distribution
• Location of Nodes
→ It will most likely indicate where the pathology is
→ Basis of lymphatic drainage
▪ Ex. Cervical Node
o Drains the upper part of the head
▪ Ex. Axillary Node
o Think breast and as such it may be warranted to do
a breast exam
Signs of Malignancy or Inflammation
• Age > 50 = more malignant than benign
• Tenderness and/or painful = usually inflammatory
→ This is a good sign as it is most likely not cancer
• Large, painless, mobile, firm, rubbery, discrete = lymphoma
• Supraclavicular Node / Scalene LAD = abnormal
• Hard, non-tender, non-movable = metastasis
Implications of a Palpable Lymph Node
• Cervical Node: it’s fine, might just be an infection
• Supraclavicular Node: bad/ suspicious
• Axillary Node: bad/ suspicious
• Epitrochlear Area: bad/ suspicious
→ Usually indicative of leukemia or lymphoma
• Inguinal Area: it depends
→ If small: it’s fine (< 2cm)
→ If large: refer for further investigation
Figure 3. Lymph Nodes in the Body
[From 2022] Spleen is considered the “largest lymph node”. Axillary,
brachial, and popliteal should not be palpable; otherwise, order
workups (i.e. biopsy) immediately (Tee, 2018)
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 E. LABORATORY INVESTIGATION • Antibody synthesis in the white pulp
• Removal of antibody-coated bacteria and antibody-coated
NOTE
blood cells from the circulation
• Doc did not specifically explain each laboratory test and as such
additional explanations were sourced from Kasper (2015)
Gross Anatomy
• Normal Spleen
• Complete Blood Count → Mass: less than 250g (<250g)
 Can provide useful data for diagnosis of acute or chronic → Diameter: 13 centimeters
leukemias, EBV or CMV mononucleosis, lymphoma with a  Location: lies relative to the 9th to 11th rib at the left upper
leukemic component, pyogenic infections, or immune quadrant
cytopenias in illnesses such as SLE
• Imaging Studies B. PHYSICAL EXAMINATION
 Important for visualizing those nodes that are not normally Inspecting for Splenomegaly Video
palpable (e.g. mediastinal, paracaval, portal nodes, etc.) https://www.youtube.com/watch?v=dzrPuy_bszc
 CT and MRI
• Note: Before proceeding, Doc Tee only showed the video for
 65-90% accurate in the diagnosis of metastasis to
inspection, percussion, and palpation of the spleen in class and
cervical lymph nodes
did not expound that much on the Physical Examination part. All
 Other modalities used are ultrasound and color Doppler
information below was lifted from the 2022 Trans to supplement
ultrasonography
the video. Feel free to skip.
• Serological studies to confirm suspicion
 May demonstrate antibodies specific to EBV, CMV, HIV, and
other viruses Percussion
▪ E.g. HIV Screening  Two techniques to help detect splenomegaly
▪ E.g Monospot Tests (Eptein-Barr Virus)  Percussing the Traube’s Space
• Lymph Node Biopsy  Checking for the Splenic Percussion sign
 Prompt biopsy should occur if patient’s and physical findings
suggest a malignancy Percussing the Traube’s Space
 E.g. A solitary, hard, nontender cervical node in an older
 Traube’s Space is found at the left lower anterior chest wall from
patient who is a chronic tobacco user
the border of cardiac dullness at the 6th rib to the anterior axillary
 E.g. Supraclavicular adenopathy
line and down to the costal margin
 E.g. Solitary or generalized adenopathy that is firm,
 If dull = positive splenomegaly
movable, suggestive of lymphoma
 If tympanic = negative splenomegaly
 Fine-needle aspiration should be reserved for thyroid
nodules and confirmation of relapses only

III. APPROACH TO A PATIENT WITH SPLENOMEGALY

A. SPLENOMEGALY

Figure 5. In percussion, dullness should not be heard along the

Traube’s Space in a normal patient. When the spleen enlarges
enough, upon percussion, it covers the area beneath the Traube’s
space making one hear a dull sound rather than tympanic (Bickley,
2013)

Checking for Splenic Percussion Sign

 Area of the lowest interspace in the left anterior axillary line should
be tympanic when percussed
 Ask the patient to take a deep breath then percuss
 If normal = tympanic
 If with splenomegaly = percussion shifts from tympanic to dull
Figure 4. Comparison of a Normal Spleen and a Massive Spleen after inspiration

• Splenomegaly is the enlargement of the spleen

→ May enlarge to 10 or more times its normal size and weight
→ Spleen is not normally palpable

Common Signs and Symptoms of Splenomegaly

• Heaviness or Left Upper Quadrant (LUQ) fullness
• Early satiety
→ Due to spleen taking up the space of the stomach

SPLENOMEGALY AS A HEMATOLOGIC REACTION
 Splenomegaly is a hematologic reaction because the spleen is
a hematopoietic organ. Hence, any malignancies or deficiencies
related to synthesis or abnormal proliferation of blood
components would also affect the spleen.
  Using the left hand, reach over and around the patient to
Normal Spleen
 Largest of the lymphatic organs
• Participates in the body’s defense system as a site of lymphocyte
proliferation and of immune surveillance and response
Functions
• Removal of senescent RBCs
 Maintenance of quality control over
erythrocytes
Figure 6. Negative Percussion sign with tympanic sounds before and
after inspiration (Bickley, 2013)
Palpation
 Sequence
support and press forward the lower left rib cage and adjacent
soft tissue.
 Begin palpation low enough so that you are below a possible
enlarged spleen.
 Ask patient to take a deep breath.
 Enlarged spleen can be felt at the edge of the examiner’s
fingertips.

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 V. APPROACH TO A BLEEDING PATIENT AND A PATIENT
WITH PATHOLOGIC CLOTTING
A. REVIEW OF HEMOSTASIS AND THROMBOSIS
 Hemostasis is a precisely orchestrated process involving platelets,
clotting factors, and endothelium that occurs at the site of vascular
injury and culminates in the formation of a blood clot, which serves
to prevent or limit the extent of bleeding

Arterial Vasoconstriction
 This occurs immediately and reduces blood flow to injured area
Figure 7. Enlarged spleen is palpable below the left costal  This is mediated by reflex neurogenic mechanisms and augmented
margin upon inspiration of the patient (Bickley, 2013) by local secretion of factors such as endothelin
→ Endothelin is a potent, endothelium-derived vasoconstrictor
 Repeat the patient lying on the right side with legs flexed at  Effect is transient, and bleeding would resume if not for the
the hips and the knee. platelets and coagulation factors
 In this position, gravity may bring the spleen forward and
to the right in a palpable location. Primary Hemostasis
• Disruption of endothelium exposes the following:
→ Subendothelial von Willebrand factor (vWF)
→ Collagen that promotes platelet adherence and activation
▪ Activation of platelets results in
o Transformation of platelets from small rounded
discs to flat plates with spiky protrusions that
markedly increase surface area
o Release of secretory granules
• Within minutes, the secreted products recruit additional platelets
→ These platelets undergo aggregation to form a primary
hemostatic plug
▪ The primary hemostatic plug is not stable and easily
Figure 8. The enlarged spleen is palpable about 2cm below the left soluble
costal margin upon inspiration (Bickley, 2013) • Bleeding of mucosal surfaces would indicate problems with primary
hemostasis
C. DISEASES ASSOCIATED WITH SPLENOMEGALY
Diseases
• Chronic Myeloid Leukemia (CML)
• Lymphomas
• Hairy Cell Leukemia
• Myelofibrosis with Myeloid Leukemia
• Polycythemia Vera
• Gaucher’s Disease
→ Type of storage disease
→ Absence of glucocerebrosidase which breaks down
glucocerebroside
→ Results to accumulation of substance in liver, spleen, bone
marrow, and nervous system
• Chronic Lymphocytic Leukemia (CLL)
• Sarcoidosis
• Autoimmune Hemolytic Anemia (Diffuse Splenic
Hemangiomatosis) Figure 9. Primary hemostasis (Kumar et. al., 2015)
• Infections (EBV, Malaria, CMV)
Secondary Hemostasis
MNEMONIC: CHINA Mobile Phone Sucks • Tissue factor is also exposed at the site of injury
• CHINA Mobile Phone Sucks → Tissue factor is a membrane-bound procoagulant
→ C-CML, CLL glycoprotein that is normally expressed by subendothelial
→ H-airy Cell Leukemia cells in the vessel wall (e.g. smooth muscle cells and
fibroblasts)
→ I-nfections (EBV, Malaria, CMV)
→ Tissue factor binds with factor VII which stimulates factor X
→ N-eoplasm (Lymphomas)
and factor Va which bind together to convert prothrombin to
→ A-uto Immune Hemolytic Anemia
thrombin
→ M-yelofibrosis with Myeloid Leukemia
• Thrombin cleaves circulating fibrinogen into insoluble fibrin,
→ P-olycythemia Vera creating a fibrin meshwork (also a potent activator of platelets)
→ S-arcoidisis → This leads to additional platelet aggregation at the site of injury
▪ This sequence consolidates the initial platelet plug
IV. APPROACH TO A PATIENT WITH WBC • Bleeding in joints and muscles will be caused by a problem of
ABNORMALITIES secondary hemostasis
A. LEUKEMIA
• Cancer of the blood
• Much of symptoms is a consequence bone marrow failure and
patients with leukemia will produce an abnormal/immature WBCs

Signs and Symptoms

• Includes non-specific signs and symptoms because of
cytopenias:
→ Lack of WBCs
▪ Fevers and infections
→ Anemia due to lack of RBCs
▪ fatigability
→ Bleeding due to lack of platelets
• Usually diagnosed as a constellation of signs and symptoms

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 B. DIAGNOSTIC APPROACH TO A BLEEDING PATIENT
Medical History
• A detailed history and physical examination are the most
important components in approaching a bleeding patient
 A history of bleeding is the most important predictor of bleeding
risk

Other Important Questions to Ask on During The History Taking

• Spontaneous or trauma-induced bleeding?
 Example questions for trauma/injury-induced:
o “Noong nasugatan po ba kayo, kinakailangan po ba
ninyong pumunta sa ospital dahil sa sobrang pagdurugo/
hindi tumitigil na pagdurugo?”
 Spontaneous hemarthrosis are a hallmark of moderate and
severe factor VIII and IX deficiency (Kasper et al., 2015)
• Previous surgery/dental procedures
→ Ask about excessive bleeding during previous surgeries
→ Example: circumcision, dental extraction, appendectomy
• Easy bruising and epistaxis
→ Ask about severity, frequency, duration and laterality
• Stools
→ Melena = dark black, tarry feces that are associated with
upper gastrointestinal bleeding
→ Hematochezia = passage of fresh blood through the anus,
seen in stools
• Menstrual history
Figure 10. Clotting in the laboratory (Kumar et. al., 2015)
→ Does the patient experience:
▪ Menorrhagia (amount)
o Abnormally heavy/prolonged bleeding
o Defined quantitatively as a loss of >80mL of blood
per cycle, based on blood loss required to produce
iron deficiency anemia (Kasper et. al., 2015)
o “how many pads do you use?”; “use maxi pads?”
▪ Metrorrhagia (time)
o Menstrual bleeding that occurs at frequent, irregular
intervals
▪ Menometrorrhagia (amount and time)
o Excessive and prolonged uterine bleeding that
occurs at irregular, frequent intervals
• Post-partum hemorrhage
• Family history of bleeding
→ A detailed personal and family history is key in determining
the chronicity of symptoms and the likelihood of the disorder
Figure 11. Secondary Hemostasis (Kumar et.al., 2015) being inherited
• Underlying systemic diseases
Clot Stabilization and Resorption
→ Liver disease
NOTE: Doc just brushed over this part
▪ This condition affects production of coagulation factors
• We need a way to stop clotting and remodeling to prevent formation
and thrombopoietin since liver is the one producing them
of aberrant clots as well as limit clotting at the sites of injury
→ Renal disease
→ Anticoagulants
▪ Accumulation of Urea causes platelets to not stick
▪ Protein C
together
▪ Protein S
→ Nephritic syndrome
▪ Antithrombin
▪ This condition leads to loss of coagulation factors in urine
→ Fibrinolytic activity
• Medications
▪ t-PA (tissue plasminogen activator) which activates
→ Some drugs may cause increased bleeding
fibrinolysis
▪ Anti-platelets (e.g. Aspirin)
▪ NSAIDS
o Inhibits cyclooxygenase 1 which will inhibit the
production of thromboxane, which is needed in
platelet aggregation (Tee, 2019)
→ Many herbal supplements can also impair hemostatic function
(see Table 1)

Table 1. Herbal supplements associated with increased bleeding (Bold

= mentioned by doc) (Tee, 2019)
Herbal Supplements
Herbs with potential Coumarin-containing herbs
antiplatelet activity
• Ginko • Motherwort
• Garlic • Chamomile
• Dong quai • Fenugreek
• Turmeric • Horse chestnut
• Bilberry • Red clover
• Ginger
• Fevervew
• Asian Ginseng
Figure 12. Anticoagulant and Fibrinolytic Effects (Kumar et. al., 2015) • Siberian Ginseng/elutheo
• Meadowsweet
• Willow

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 Physical Examination C. DIAGNOSTIC APPROACH TO A PATIENT WITH
• Determine the location of bleeding: PATHOLOGIC CLOTTING
 If mucosal = defect in the primary hemostasis • See Appendix Table 8
▪ Platelet problem leading to profuse bleeding • Thrombosis
▪ E.g. Gum bleeding → Formation of clots at unusual sites (Tee, 2019)
→ If located at the joints and muscle = defect in the secondary → Can either be arterial or venous thrombosis
hemostasis (Tee, 2019) • Arterial thrombosis
▪ Example of disease: Hemophilia
→ Platelets are normally involved
• Skin lesions:
→ May be due to atherosclerosis (major risk factor) (Kasper et
→ Petechia al., 2015)
▪ Tiny, non-blanchable macules resulting from tiny
• Venous thrombosis
hemorrhages that are usually 1-2mm in diameter
→ Tissue factors are usually involved
→ Hematoma
▪ May be due to immobility, surgery, underlying medical
▪ Mass of clotted blood that forms in an organ, space, or
conditions (malignancy), medications, therapy, obesity,
in the tissues
and genetic predispositions (Kasper et al., 2015)
→ Ecchymoses
▪ Palpable, bluish-purple blanching macule or patch that Virchow’s Triad
usually occurs as a result of trauma
• Useful in determining the factors that contribute to thrombosis
• NOTE: Sir just mentioned the categories, additional info was added
Laboratory Tests
for better understanding
• No laboratory test can evaluate global hemostatic competence
→ History taking is really your best tool! Three Categories
Screening Test • Hypercoagulability
→ Includes risk factors that can cause the excessively easy
• Complete blood count
clotting of blood (e.g. major surgery/trauma, estrogen therapy,
• Peripheral Smear inflammation, dehydration, malignancy, etc.)
→ Especially if suspecting thrombocytopenia • Circulatory stasis
• Prothrombin Time → Includes alterations that disrupt normal blood flow (e.g.
 May detect liver disease or vitamin K deficiency if the time is venous obstructions, prolonged immobility, varicose veins,
abnormal low blood pressure, bradycardia, congenital defects in venous
• Partial Thromboplastin Time anatomy, etc.)
→ If abnormal, it may indicate a problem with Heparin • Vascular wall injury
• Specific Factor Assays → Includes injuries and/or trauma to the blood vessel wall (e.g.
• Bleeding time and clotting time physical trauma, strain or injury, microtrauma to vessel wall)
Thrombocytopenia
• Mechanisms of low platelet count:
→ Decreased production of platelets
▪ Aplastic anemia
▪ Bone marrow infiltration/ myelopthisis
o Myelopthisis is the replacement of hematopoietic
tissue in the bone marrow by abnormal tissue,
usually by fibrous tissue or malignant tumors
→ Increased sequestration
▪ Hypersplenism
→ Increased destruction
▪ Immune-mediated thrombocytopenia
▪ Drug induced
▪ Infections

Figure 13. Virchow’s triad (Thrombosis Advisor, 2019)

Medical History
• Upon history taking, we may note if the thrombosis is provoked or
unprovoked
→ Provoked
▪ There is a stimulus causing it such
▪ E.g. Being immobilized (sitting on a plane) for 18 hours
→ Unprovoked
▪ Spontaneous and can re-occur
▪ Strongest predictor in recurrence of venous
thrombosis

Risk Factors for Thrombosis

• Family history
→ Most of thrombophilia may be genetic
→ Ask for early MI or Stroke
• Age
• Gender
→ Clotting happens more in Males
• Medications
Figure 12. Algorithm for thrombocytopenia evaluation (Kasper et al., → Pills may cause thrombosis
2015) Note: Normal Platelet count is 150,000-450,000 • Hospitalization due to surgery
• Obesity
• Smoking

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• NOTE: See Table 2 for complete list ▪ Size and texture of nodes
Table 2. Risk Factors for Thrombosis (Kasper et al., 2015) ▪ Distribution
Venous Venous and Arterial ▪ Location of nodes
Inherited ▪ May give clues on the cause of the lymphadenopathy
• Factor V Leiden • Homocystinuria → Laboratory Test
• Prothrombin G2021A • Dysfibrigonemia ▪ Complete Blood Count (CBC)
• Antithrombin deficiency ▪ Serologic Studies
• Protein C deficiency ▪ Imaging Techniques
o CT and MRI
• Protein S deficiency
▪ Lymph node biopsy
• Elevated factor VIII
• Splenomegaly
Acquired
→ Enlargement of the spleen
• Age • Malignancy
→ Massive splenomegaly
• Previous thrombosis • Antiphospholipid antibody ▪ When the spleen extends into the left lower quadrant or
• Immobilization syndrome pelvis or crosses the midline of the abdomen
• Major surgery • Hormonal therapy → Signs and Symptoms
• Pregnancy and puerperium • Polycythemia vera ▪ Heaviness or left upper quadrant fullness
• Hospitalization • Essential thrombocytopenia ▪ Early satiety
• Obesity • Paroxysmal nocturnal → Spleen
• Infection hemoglobinuria ▪ Largest lymphoid organ
• APC resistance, nongenetic • Thrombotic thrombocytopenic ▪ Function of the spleen
• Smoking purpura o Maintenance of quality control over erythrocytes. 

• Heparin-induced o Synthesis of antibodies
thrombocytopenia o The removal of antibody-coated bacteria and
• Disseminated intravascular antibody-coated 
blood cells
coagulation ▪ Normal mass: 250 grams
Others Mixed ▪ Normal diameter: 13 cm
• Elevated factor II, IX, XI • Hyperhomocysteinemia ▪ Normal location of the spleen: lies relative to the 9th and
• Elevated TAFI levels 11th rib 
at the LUQ
• Low levels of TFPI → Physical Examination
▪ Percussion of Traube’s space
Laboratory Test o In normal patients, percussion remains tympanitic
• Variables tested o In patients with splenomegaly, percussion shifts
→ Protein C, Protein S from tympanic 
to dull after inspiration
→ Antithrombin III ▪ Palpation
▪ Prothrombin G2021 mutation o Enlarged spleen is usually palpable at below the
▪ Factor V Leiden left costal margin upon inspiration of the patient
▪ APAS panel → Associated diseases with splenomegaly
▪ Factor VIII levels ▪ Chronic myeloid leukemia
• Repeat the testing ▪ Lymphomas
→ After an acute event ▪ Hairy cell leukemia
→ After the patient is off their medication ▪ Myelofibrosis with myeloid leukemia
▪ Polycythemia vera
QUICK REVIEW ▪ Gaucher’s disease
SUMMARY OF TERMS ▪ Chronic lymphocytic leukemia
• Polycythemia ▪ Sarcoidosis
→ Body tries to compensate for oxygen by increasing RBC ▪ Autoimmune hemolytic anemia
production • Leukemia: consequence of bone marrow failure
→ Medical History:
▪ Conditions of reduced oxygen uptake Table 3. Hemostasis
→ Risk Factors: Hemostasis
▪ Smoking Arterial • Reduced blood flow
▪ High altitude Vasoconstriction • Mediated by reflex neurogenic
▪ Lung or Heart disease mechanisms
▪ Sleep apnea • Augmented by local secretion of factors
→ Other Symptoms: • Transient
▪ Headache Primary • Exposure of von Willebrand factor and
▪ Vertigo hemostasis collagen
▪ Aquagenic pruritus • Results in dramatic shape change
▪ Visual disturbances • Recruits additional platelets within
→ Physical Examination minutes
▪ Flushing • Form a primary hemostatic plug
▪ Heart murmurs Secondary • Tissue factor is also exposed at the site
▪ Lung sounds Hemostasis of injury
▪ Cyanosis • TF activates factor VII
▪ Abdominal pain • Thrombin is generated and cleaves the
→ Lab tests circulating fibrinogen into fibrin
▪ Increased hemoglobin or hematocrit. • A fibrin meshwork is made
▪ Elevated WBC count
Clot stabilization • Polymerized fibrin and platelet
▪ Increased absolute basophil count
and resorption aggregation undergo contraction to form
▪ Thrombocytosis
a permanent plug that prevents further
▪ Usually low levels of EPO
hemorrhage
• Lymphadenopathy

• Limits the clotting only to the site of the
→ Enlargement of the lymph nodes injury
→ Medical history:
▪ Concurrent illnesses and symptoms Table 4. Tissue Factor
▪ Age Tissue Factors
▪ Sex
Intrinsic VIII, IX, XI, XII
▪ Personal and social history
Extrinsic VII
→ Physical Examination

YL6: 04.17b Basic Pathologies 2: Approach to a Patient with Hematologic Alterations 7 of 9

Table 5. Diagnostic approach to bleeding patient 7. Which of the following exemplifies the the extrinsic pathway?
Diagnostic Approach a) TFVIIa > X > Xa > prothrombin > thrombin > fibrinogen > fibrin
Detailed History • History of bleeding b) TFIXa > X > Xa > prothrombin > thrombin > fibrinogen > fibrin
• Bleeding spontaneous or trauma- c) TFIXa > X > Xa > thrombin > prothrombin > fibrinogen > fibrin’
induced d) TFVIIa > X > Xa > thrombin > prothrombin > fibrinogen > fibrin
• Previous surgeries/dental procedures 8. What is the most important component in approaching a bleeding
• Bruising patient?
• Epistaxis a) Laboratory test
b) Medical History
• Menstrual history
c) Physical Exam
• Family history of bleeding
d) Screening test
• Underlying systemic diseases e) Both B and C
• Medications 9. TRUE or FALSE: Arterial thrombosis typically involves tissue
Physical • Location of bleed factors while venous thrombosis involves platelets and may be due
Examination • Petechiae to atherosclerosis
• Hematoma 10. What is NOT included in the three categories of Virchow’s Triad?
• Ecchymoses a) Hypocoagulability
Screening Tests • Complete blood count b) Circulatory Stasis
• Peripheral smear c) Vascular wall injury
• Prothrombin time
• Partial Thromboplastin time Answers (if self-explanatory)
• Specific Factor assays 1C, 2B, 3E, 4C, 5D, 6C, 7A, 8E, 9F, 10A
• Bleeding time and clotting time
REFERENCES
MNEMONICS REQUIRED
(1) ASMPH Batch 2023. 2019. Trans Format.
MNEMONIC: CHINA Mobile Phone Sucks (2) Bickley, Lynn S. (2013). Bates' guide to physical examination and
• CHINA Mobile Phone Sucks history taking. Philadelphia: Lippincott Williams & Wilkins.
→ C-CML, CLL (3) Kasper et al. (2015). Harrison’s principles of internal medicine. US:
→ H-airy Cell Leukemia McGraw-Hill Education.
→ I-nfections (EBV, Malaria, CMV) (4) Kumar et al. (2015). Robbins and Cotran: Pathologic basis of
→ N-eoplasm (Lymphomas) disease. Philadelphia: Elsevier.
→ A-uto Immune Hemolytic Anemia (5) Thrombosis Advisor. Thrombus Formation - Virchow's Triad &
→ M-yelofibrosis with Myeloid Leukemia Types of Thrombi, https://www.thrombosisadviser.com/thrombus-
→ P-olycythemia Vera formation/. October 10, 2019.
→ S-arcoidisis (6) Kurzrock, R. (2001). The role of cytokines in cancer-related fatigue.
Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11598887.

REVIEW QUESTIONS IMPORTANT LINKS

1. Tonito, a 20-year-old male who has a history of sleep apnea has
increased hemoglobin levels (>170g/L), elevated RBC mass and Trans feedback: https://tinyurl.com/AcadsTransFeedback
low serum EPO levels. What does Tonito most likely have? Errata submission: https://tinyurl.com/ContentErrataSubmission
a) Macrocytic Anemia Errata tracker: https://tinyurl.com/ErrataTracker
b) Splenomegaly
c) Polycythemia
d) Proliferative Anemia
2. Tristan was recently diagnosed with lymphadenopathy, which of APPENDIX
the following signs is NOT an indicator to his disease being Table 7. Diseases Associated with Lymphadenopathy
malignant? NOTE: Doc said no need to memorize all the diseases in the table, those
a) Tristan is >50 years old in Bold are the ones Doc mentioned in class
b) Lymph nodes are tender and painful Type Specific Disease
c) Lymph nodes are hard, non-tender and non-movable Infectious • Viral—
d) Lymph node is palpable at the supraclavicular area Diseases o Infectious Mononucleosis
3. Which of the following tests would you do for Tristan if his physical Syndromes (EBV, CMV)
findings do suggest malignancy? o Infectious Hepatitis
a) CBC o Herpes Simplex
b) Imaging studies o Herpesvirus-6
c) Serological studies o Varicella-Zoster Virus
d) Lymph node biopsy o Rubella
e) Both B and D o Measles
4. Which of the following is NOT a sign of splenomegaly? o Adenovirus
a) Early satiety o HIV
b) Heaviness in the Left Upper Quadrant o Epidemic Keratoconjunctivitis
c) Spleen is 230g with a diameter of 13 inches o Vaccinia
d) Traube’s space is dull upon percussion o Herpesvirus-8
5. Which of the following diseases is NOT associated to • Bacterial—
splenomegaly? o Streptococci
a) Hairy Cell Leukemia o Staphylococci
b) Lymphoma o Cat-scratch Disease
c) EBV infection o Brucellosis
d) Diabetes o Tularemia
6. Primary hemostasis happens when the disruption of the o Plague
endothelium exposes collagen and vWF which promotes platelet o Chancroid
adherence and activation. These platelets undergo aggregation to o Melioidosis
form a plug that is stable and insoluble. Which of the statements o Glanders
are true? o Tuberculosis
a) Both statements are TRUE o Atypical Mycobacterial Infection
b) Both statements are FALSE o Primary and Secondary Syphilis
c) The first statement is true and the second is false o Diphtheria
d) The first statement is false and the second is true o Leprosy
o Bartonella

YL6: 04.17b Basic Pathologies 2: Approach to a Patient with Hematologic Alterations 8 of 9

 • Fungal— Prolonged Prothrombin Time (PT)
o Histoplasmosis • Factor VII deficiency
o Coccidioidomycosis • Vitamin K deficiency – early
o Paracoccidioidomycosis • Warfarin anticoagulation
• Chlamydial— • Direct Xa inhibitors (Rivaroxaban, apixaban)
o Lymphogranuloma Venereum Prolonged PTT and PT
o Trachoma • Factor II, V, X, or fibrinogen deficiency
• Parasitic • Vitamin K deficiency – Late
o Toxoplasmosis • Direct thrombin inhibitors
o Leishmaniasis Prolonged Thrombin Time
o Trypanosomiasis
• Heparin or heparin-like inhibitors
o Filariasis
• Direct thrombin inhibitors (e.g. dabigatran, argatroban,
• Rickett
bivalirudin)
o Scrub Typhus
o Rickettsialpox • Mild or no bleeding – dysfibrinogenemia
• Q fever • Frequent, severe bleeding – afibrinogenemia
Prolonged PT and/or aPTT not corrected with Mixing with
Immunological • Rheumatoid Arthritis
Normal Plasma
Diseases • Juvenile Rheumatoid Arthritis
• Bleeding – specific factor inhibitor
• Mixed Connective Tissue Disease
• No symptoms, or clotting and/or pregnancy loss – lupus
• Systemic Lupus Erythematosus
anticoagulant
• Dermatomyositis
• Disseminated intravascular coagulation
• Sjogren’s Syndrome
• Heparin or direct thrombin inhibitor
• Serum Sickness
Abnormal Clot Solubility
• Drug Hypersensitivity—diphenylhydantoin,
hydralazine, allopurinol, primidone, gold, • Factor XIII deficiency
carbamazepine, etc. • Inhibitors or defective cross-linking
• Angioimmunoblastic Lymphadenopathy Rapid Clot Lysis
• Primary Biliary Cirrhosis • Deficiency of a2-antiplasmin or plasminogen activator inhibitor 1
• Graft-versus-host Disease • Treatment with fibrinolytic therapy
• Silicone-associated
• Autoimmune Lymphoproliferative FREEDOM SPACE
Syndrome
• IgG4-related Disease
• Immune Reconstitution Inflammatory
Syndrome (IRIS)
Malignant • Hematologic—
Diseases o Hodgkin’s Disease
o Non-Hodgkin’s Lymphomas
o Acute or Chronic Lymphocytic
Leukemia
o Hairy Cell Leukemia
o Malignant Histiocytosis
o Amyloidosis
• Metastatic— cancer from different/
numerous primary sites
Lipid Storage • Gaucher’s
Diseases • Niemann-Pick
• Fabry
• Tangier
Endocrine • Hyperthyroidism
Diseases
Others • Castleman’s Disease (Giant Lymph Node
Hyperplasia)
• Sarcoidosis
• Dermatopathic Lymphadenitis
• Lymphomatoid Granulatosis
• Histiocytic Necrotizing Lymphadenitis
(Kikuchi’s Disease)
• Sinus histiocytosis with massive
lymphadenopathy (Rosai-Dorfman
disease)
• Mucocutaneous lymph node syndrome
(Kawasaki’s disease)
• Histiocytosis X
• Familial Mediterranean fever
• Severe hypertriglyceridemia
• Vascular transformation of sinuses
• Inflammatory pseudotumor of lymph node

Table 8. Hemostatic Disorders and Coagulation Test Abnormalities

(Tee, 2019)
Prolonged Activated Partial Thromboplastin Time (aPTT)
• No clinical bleeding - ↓ factor XII, high-molecular-weight
kininogen, prekallikrein
• Variable, but usually mild, bleeding - ↓ factor XI, mild ↓ factor VIII
and factor IX
• Frequent, severe bleeding – severe deficiencies of factors VIII
and IX
• Heparin and direct thrombin inhibitors

YL6: 04.17b Basic Pathologies 2: Approach to a Patient with Hematologic Alterations 9 of 9